MS news and research
This page documents breaking multiple sclerosis news and research stories as they occur during the month.
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St. Lawrence University professors and recent graduates have discovered a type of nanoparticle that may alleviate symptoms of multiple sclerosis.
Karin Heckman, assistant professor of biology, and William E. DeCoteau, associate professor of psychology, were lead authors on a research paper, published in a scientific journal, that examined cerium oxide nanoparticles and their ability to alleviate the symptoms of multiple sclerosis.
The article, titled “Custom Cerium Oxide Nanoparticles Protect Against a Free Radical Mediated Autoimmune Degenerative Disease in the Brain,” was published this month in ACS Nano, a publication of the American Chemical Society.
Ana Y. Estevez, associate professor of biology and psychology, and Joseph S. Erlichman, professor and R. Sheldon ’68 and Virginia H. Johnson Chair of Science and co-chair of the Department of Biology, were also listed as authors in the publication.
The study concluded that cerium oxide nanoparticles are widely used as catalysts in industrial applications and are considered potent antioxidants due to their free radical-scavenging properties.
Heckman, DeCoteau, and the other author’s laboratory experiments indicate the particular set of particles located in research at St. Lawrence University have the potential to alleviate the symptoms of multiple sclerosis, a neurodegenerative disease, while not causing damage to the liver and spleen of mice.
“St. Lawrence has a unique set of cerium oxide particles,” said Heckman, who specializes in infections and autoimmune diseases. “These particles move into the brain to help to provide therapy. Yet, these particles also diminish over time.”
Heckman also recently attended a Sustainable Nanotechnology Organization conference earlier this month in Santa Barbara, Calif., where she delivered a presentation titled “Differences in the Neuroprotective Effects of Nanoceria in a Murine Model of Multiple Sclerosis,” and tested St. Lawrence’s particle research against other commercially available products.
The presentation mirrored the recently published paper.
Heckman was joined at the conference by Associate Professor of Chemistry Matthew C. Skeels, DeCoteau and Erlichman.
Heckman said ultimately the development of a pharmaceutical drug is the goal.
“The question we’re asking now is how can these particles be used therapeutically if they’re packaged in the correct chemical form,” she said. “It can take up to 10 years for a drug to be fully developed, from the initial research to FDA (U.S. Food and Drug Administration) approval. But, yes, that’s the goal.”
According to Heckman, former St. Lawrence University students were instrumental in the study, monitoring experiments twice a day and conducting a series of motor tests on laboratory mice.
Source: North Country Now ©North Country 2013 (09/12/13)
NICE recommends new oral MS drug Aubagio(06/12/13)
NICE has recommended that the national health service use Sanofi's new multiple sclerosis pill Aubagio, which will be supplied at a discount.
The National Institute for Health and Clinical Excellence (NICE) - the body that decides if drugs should be paid for - said on Friday its final draft guidance recommended Aubagio, or teriflunomide, for adults with relapsing-remitting multiple sclerosis.
The drug's list price is 13,529 pounds per patient a year but the size of the discount has not been disclosed.
On Thursday, NICE said it needed more information before deciding if a separate Sanofi drug for the disease, Lemtrada, was worth using.
Source: Reuters Copywrite Thomson Reuters 2013 (06/12/13)
Teva Pharmaceutical has licensed rights to commercialize glatiramer acetate to Takeda Pharmaceutical in Japan as part of their agreement signed earlier in 2013.
Currently both the firms are working on additional agreements for implementation of the license.
Developed by Teva, glatiramer acetate for injection is indicated for the relapse prevention of multiple sclerosis and is marketed under the brand name Copaxone.
The drug is considered standard treatment for relapsing-remitting multiple sclerosis including patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.
It is currently approved in 55 countries worldwide, including the US, Russia, Canada, Mexico, Australia, Israel, and all European countries.
Under the deal, Teva will grant Takeda commercialization rights in Japan, and Takeda will submit a New Drug Application (NDA) for registration of glatiramer acetate in Japan.
Both the firms will work together to provide a new treatment options to patients with multiple sclerosis in Japan as early as possible, where the current available therapies are still limited.
Source: PBR © PBR 2013. (06/12/13)
The U.K.’s health-cost regulator asked Sanofi for more information on its multiple-sclerosis drug Lemtrada, less than a month after U.S. regulatory advisers said the drug’s trials weren’t adequate to assess its efficacy.
The National Institute for Health and Care Excellence is seeking clarifications on the evidence Paris-based Sanofi’s Genzyme unit submitted on the drug, NICE said in draft guidance today. Sanofi has until Jan. 9 to submit the extra information, the institute said. NICE, which advises the U.K.’s National Health Service on which treatments provide value for money, didn’t specify what information it requested.
Lemtrada, approved in the European Union in September, was a key part of Sanofi’s $20 billion acquisition of Genzyme in 2011. The U.S. Food and Drug Administration is expected to decide by the end of this year whether to approve the drug, which will compete in an increasingly crowded market against treatments such as Novartis AG’s Gilenya and Teva Pharmaceutical Industries Ltd’s Copaxone.
Lemtrada may generate sales of 455 million euros ($619 million) in 2017, according to the average of eight analysts’ estimates compiled by Bloomberg. Bayer AG (BAYN) plans to co-promote the drug in the U.S. and will receive payments based on sales. Sanofi said in October it would charge 8,645 euros per vial for the drug in Germany.
Sanofi fell 0.3 percent to 74.71 euros as of 11:39 a.m. in Paris. The stock has gained 8 percent this year, including reinvested dividends, compared with a 25 percent advance in the Bloomberg Europe Pharmaceuticals Index.
The drug is a so-called monoclonal antibody administered to patients through two sets of infusions a year apart. Late-stage clinical trials showed the treatment slowed the progression of disability, though it also led to infections and an autoimmune thyroid-related side effect in some patients.
Sanofi’s first MS therapy, a tablet called Aubagio, won approval in the U.S. last year and in the EU this year. The drugmaker is counting on new products to offset revenue losses from generic competition to best-sellers including the blood-thinner Plavix.
Multiple sclerosis is a debilitating disease that attacks the central nervous system. Relapses, or flare-ups, are episodes of worsening neurological function. More than 100,000 people in the U.K. have the disease, according to the Multiple Sclerosis Trust.
An FDA advisory committee voted last month that Lemtrada is effective for preventing flare-ups of the disease, even as it decided the company’s trials weren’t adequate to assess the drug.
Source: Bloomberg ©2013 BLOOMBERG L.P.(05/12/13)
For some, the disease multiple sclerosis (MS) attacks its victims slowly and progressively over a period of many years. For others, it strikes without warning in fits and starts. But all patients share one thing in common: the disease had long been present in their nervous systems, hiding under the radar from even the most sophisticated detection methods. But now, scientists at the Gladstone Institutes have devised a new molecular sensor that can detect MS at its earliest stages -- even before the onset of physical signs.
In a new study from the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, scientists reveal in animal models that the heightened activity of a protein called thrombin in the brain could serve as an early indicator of MS. By developing a fluorescently labeled probe specifically designed to track thrombin, the team found that active thrombin could be detected at the earliest phases of MS -- and that this active thrombin correlates with disease severity. These findings, reported online in Annals of Neurology, could spur the development of a much-needed early-detection method for this devastating disease.
MS, which afflicts millions of people worldwide, develops when the body's immune system attacks the protective myelin sheath that surrounds nerve cells. This attack damages the nerve cells, leading to a host of symptoms that include numbness, fatigue, difficulty walking, paralysis and loss of vision. While some drugs can delay these symptoms, they do not treat the disease's underlying causes -- causes that researchers are only just beginning to understand.
Last year, Dr. Akassoglou and her team found that a key step in the progression of MS is the disruption of the blood brain barrier (BBB). This barrier physically separates the brain from the blood circulation and if it breaks down, a blood protein called fibrinogen seeps into the brain. When this happens, thrombin responds by converting fibrinogen into fibrin -- a protein that should normally not be present in the brain. As fibrin builds up in the brain, it triggers an immune response that leads to the degradation of the nerve cells' myelin sheath, over time contributing to the progression of MS.
"We already knew that the buildup of fibrin appears early in the development of MS -- both in animal models and in human patients, so we wondered whether thrombin activity could in turn serve as an early marker of disease." said Dr. Akassoglou, who directs the Gladstone Center for In Vivo Imaging Research (CIVIR). She is also a professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "In fact, we were able to detect thrombin activity even in our animal models -- before they exhibited any of the disease's neurological signs."
In laboratory experiments on mice modified to mimic the signs of MS, the team employed an Activatable Cell-Penetrating Peptide (ACPP), a special type of molecular probe that delivers fluorescent agents to a region of interest. For this study, they developed a thrombin-specific ACPP that could track thrombin activity in mice as the disease progressed. They then carefully analyzed where -- and at what stage of disease -- thrombin activity was found.
"We detected heightened thrombin activity at specific disease 'hot-spots,' regions where neuronal damage developed over time," said Gladstone Staff Research Scientist Dimitrios Davalos, PhD, associate director of the CIVIR and one of the paper's lead authors. "And when we compared those results to those of a separate, healthy control group of mice, we saw that thrombin activity in the control group was wholly absent."
"Our results are proof of principle that a thrombin-specific molecular probe could be used as an early-detection method," added former Gladstone Postdoctoral Researcher Kim Baeten, PhD, the paper's other lead author.
The team's results offered significant support for the notion that thrombin activity is directly tied to the degradation of nerve cell's myelin sheath -- and the subsequent destruction of nerve cells -- that characterizes MS. But they also shed light on what has been a long-standing mystery: the underlying molecular processes that kick-start the progression of MS.
"In the future," said Dr. Akassoglou, "this thrombin-specific ACPP could be developed to one day allow for early patient diagnosis and therapeutic intervention -- including a way to effectively monitor how patients are responding to the latest treatments."
Dimitrios Davalos, Kim M. Baeten, Michael A. Whitney, Eric S. Mullins, Beth Friedman, Emilia S. Olson, Jae Kyu Ryu, Dimitri S. Smirnoff, Mark A. Petersen, Catherine Bedard, Jay L. Degen, Roger Y. Tsien, Katerina Akassoglou. Early detection of thrombin activity in neuroinflammatory disease. Annals of Neurology, 2013; DOI: 10.1002/ana.24078
Source: ScienceDaily Copyright 2013 by ScienceDaily, LLC (05/12/13)
A tuberculosis vaccine may provide an inexpensive way to treat multiple sclerosis (MS) in the future, according to a small study published in the journal Neurology.
For a U.S. MS patient, one year of medication can cost a lofty $50,000. That's a financial burden for any budget, but for many people in developing countries the price is out entirely out of reach. Worldwide, more than 2 million people deal with the disease, which affects an estimated 350,000 Americans, according to the Multiple Sclerosis Foundation.
“MS is being seen more commonly in parts of the world where the expensive medications we’re using aren’t available,” noted Dennis Bourdette, MD, a neurologist at the Oregon Health and Science University in Portland who was not affiliated with the Neurology study.
“One of the potentially exciting things about this [vaccine] is it might represent an inexpensive therapy [for people who] can’t afford the very expensive drugs,” Dr. Bourdette added.
The vaccine used in the study contains a weakened bacterium called Bacille Calmette-Guerin (BCG), which is commonly used to protect against tuberculosis and, in varying doses, is also used to treat bladder cancer.
While the vaccine is not ready for use as an MS treatment, this week’s study highlights it as an important “avenue of research that needs active pursuit,” Bourdette said.
Fewer Brain and Spine Lesions
To test the theory that the BCG vaccine might be useful in treating MS, researchers at the Sapienza University of Rome gave the vaccine to 33 people who had MS symptoms and were at high risk for developing the disease.
Every month for six months, the researchers used MRI scans to track the growth of lesions in patients’ brains and on their spinal cords – a common indicator of MS. During the course of the study, vaccine recipients developed an average of three lesions each while those in the control group had an average of about six lesions.
For Giovanni Ristori, MD, PhD, a neurologist at the Sapienza University of Rome and author of the study, the results were a validation of more than a decade of study.
“The BCG vaccine [had] no major side effects -- it’s cheap,” Dr. Ristori said. “It’s a useful approach that you can use after the start of the disease.”
Ristori followed the vaccinated group and the control group for five years after the initial injection, collecting data on their progress. Many of the patients in both groups started taking standard MS medications like disease-modifying therapies. Over time, the vaccinated patients continued to do better than those patients who had not had the BCG vaccine.
Not Ready for Prime Time
Though the study results were statistically significant, researchers have collected data on only a small number of patients -- too small to confirm whether the treatment will be as effective in larger numbers of patients. The researchers also don’t know whether the vaccine would work by itself without the aid of other MS medications.
And, finally, because MS is a lifelong disease, it’s likely that the vaccine would need to be administered multiple times throughout a person’s life. Doctors don’t know how the body might react to more than one injection of the BCG vaccine. It’s possible that the bacterium, though weakened, could have side effects such as infection or scarring at the injection site, said Bourdette.
“I'm excited about the potential for this type of approach, but we urge patients and clinicians not to use this as a therapy for MS without further studies,” he said.
Source: Everyday Health Copyright © 2013 Everyday Health Media, LLC (05/12/13)
As people step outdoors into the bright sunshine, their pupils automatically contract. Australian scientists are making use of how this "pupil reflex" is connected to the brain as a potential new way of testing the severity of multiple sclerosis (MS).
Scientists from the Australian Center of Excellence in Vision Science (ACEVS) based at the Australian National University (ANU) have used an instrument they are developing to accurately measure the pupil responses of MS patients and have found that the pupils of MS patients respond appreciably slower, the ANU said in a press release on Thursday.
The finding opens the door to a simple and quick way of tracking the severity of MS over time: the slower the response, the worse the MS.
"Our instrument uses special patterns of flashing lights that the patient looks at for four minutes," said Professor Ted Maddess, a vision scientist at ANU who is head of the ACEVS team.
"We use infrared cameras to measure light-induced changes in the diameters of both pupils, and with computer tracking we can measure the diameter to within a micrometer 30 times a second," he said.
"We have just published the results of our study of 85 MS patients, and we find that in MS patients the pupil response is about 25 milliseconds slower than in our control group. Although the study is preliminary, we believe the test has good potential in individual patients because it can precisely measure the speed of their response to within a millisecond."
Maddess said instead of an expensive MRI to track the condition, the new method gives an accurate readout after just a few minutes. That quick and easy test might, in the future, allow MS patients to be assessed on the spot and have their medication adjusted accordingly.
Source: Global Post Copyright 2013 GlobalPost (05/12/13)
New targeted stem cell therapy looks to improve MS patients dealing with incontinence complications.
StemGenex®, the leading resource for adult adipose stem cell therapy in the US aimed at improving the lives of patients dealing with degenerative diseases today announced the newest therapy to assist patients diagnosed with Multiple Sclerosis.
According to the National MS Society, at least 80% of people with MS experience bladder dysfunction. StemGenex believes a new therapy delivering adipose derived mesenchymal cells directly to the bladder may reduce the inflammation that is causing the patient’s incontinence.
Direct bladder targeting is the latest in a series of targeted therapies StemGenex® plans to announce in the next few months for patients dealing with degenerative diseases such as Parkinson’s, Alzheimer’s, COPD and of course Multiple Sclerosis. Earlier this month StemGenex announced a new intranasal stem cell therapy. The goal of this new technique is to encourage more stem cells to travel through the blood brain barrier to target the damage caused by MS.
Stem cell treatment studies are currently being offered by StemGenex to patients diagnosed with Multiple Sclerosis and other degenerative neurological diseases. StemGenex takes a unique approach of compassion and empowerment while providing access to the latest stem cell therapies for degenerative neurological diseases including Parkinson’s and Alzheimer’s disease, stroke recovery and others. Rita Alexander, founder of StemGenex and the company’s first stem cell patient, insists that all patients be treated like they are one of our loved ones. "Hope, compassion, and the relentless pursuit for an end to these diseases are our primary focus."
Source: © Copyright 1997-2013, Vocus PRW Holdings, LLC. Vocus, PRWeb (03/12/13)
Physicians should be sure to exclude bipolar disorder before prescribing antidepressants to patients with multiple sclerosis (MS) who have depression, say researchers.
The team, led by Mauro Carta (University of Cagliari, Italy), found an increased prevalence of mood disorders among MS patients, with the relative increase largest for bipolar disorders.
Given that it can be hard to differentiate bipolar disorder, particularly type II, from major depressive disorder, the findings imply a risk for overlooking bipolarity in MS patients, say the researchers. This could lead to inappropriate treatment with antidepressants rather than mood stabilizers.
In all, 46.7% of 201 MS patients had any form of mood disorder, compared with just 5.2% of 804 age- and gender-matched controls. Major depressive disorder was most common, occurring in 26.3% of patients versus 4.6% of controls. Bipolar I disorder occurred in 0.99% versus 0% and bipolar II disorder in 7.50% versus 0.25%.
Specific disorders were based on DSM-IV criteria, but the same pattern was apparent with mood spectrum disorders detected with the broader Mood Disorder Questionnaire criteria. Overall, 27.3% of patients versus 4.9% of controls had a depressive spectrum disorder, and 9.9% versus 0.3% had a bipolar spectrum disorder.
“From a clinical perspective, we can consider that the higher risk of suicidality in MS patients could be related to possible mood episodes (included bipolar depression),” writes the team in the Journal of Affective Disorders.
Although less common than depression overall, bipolar disorder was a relatively more frequent mood disorder among the patients than controls. For each control with a bipolar spectrum disorder, 18 had a depressive condition, whereas there were just 2.8 depressive spectrum cases per bipolar case among the MS patients.
“The evidence of a strict association between MS and [bipolar disorder] is really interesting from both a clinical and a pathophysiological point of view,” say Carta et al.
Pathologic processes occurring in MS, such as oxidative stress, may mediate the link between the two conditions, they suggest.
Source: News-Medical.Net (27/11/13)
GW Pharmaceuticals plc, a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, announced that it has received regulatory approval for its prescription medicine Sativex(R) in Switzerland. A full marketing authorization has been granted by the Swissmedic authorities in the treatment of moderate to severe spasticity in Multiple Sclerosis (MS) patients who have not responded adequately to other anti-spasticity medications. Launch timing is dependent on completion of pricing and reimbursement procedures. Sativex will be commercialized in Switzerland by GW's European partner, Almirall S.A.
"This approval in Switzerland marks yet another regulatory success for Sativex, which is now approved in a total of 23 countries," stated Justin Gover, Chief Executive Officer of GW. "We now look forward to working with our partners, Almirall, towards this launch so as to enable MS patients in Switzerland to benefit from this important new treatment."
Sativex is approved for use in the treatment of MS spasticity in 23 countries, including 17 countries in Europe. The medicine is currently available on prescription in the UK, Spain, Germany, Canada, Denmark, Norway, Israel, Austria, Poland, Sweden, Italy and Finland with launches currently in preparation for a further 8 European countries, as well as Australia, New Zealand and Kuwait.
Source: GW Pharmaceuticals plc (27/11/13)
European Medicines Agency determines that dimethyl fumarate in MS drug Tecfidera qualifies as a new active substance(22/11/13)
Biogen Idec Inc. said the European Medicines Agency's Committee for Medicinal Products for Human Use determined that dimethyl fumarate in its drug Tecfidera qualifies as a new active substance.
Shares jumped 10% to $276.97 in early trading, as the designation provides 10 years of regulatory exclusivity in the European Union for the multiple-sclerosis treatment. The stock is up about 90% so far this year.
The determination follows a positive opinion by the committee in March recommending marketing authorization in the EU for the drug as a first-line treatment for adults with relapsing-remitting multiple sclerosis.
The CHMP's determination will be referred to the European Commission, which grants marketing authorization for medicines in the EU. If approved, Tecfidera will mark the fourth therapy for MS that Biogen offers in the EU.
Biogen is aiming to become the dominant maker of MS treatments, a group of drugs that command high prices and that patients typically take for years.
The U.S. Food and Drug Administration in March approved Tecfidera, one of a new class of oral pills predicted to eventually become the standard of care for MS, replacing the injectable therapies that now comprise the bulk of the market. According to IMS, Tecfidera is the leading oral MS therapy in the U.S.
Biogen has been bolstering its sales force and readying its manufacturing supply chain as some drugs in its late-stage product pipeline move closer to entering the market.
Its third-quarter earnings rose 22% on stronger sales from Tecfidera.
Source: 4-traders Copyright © 2013 Surperformance (22/11/13)
A $500,000 drug development grant from the National Multiple Sclerosis Society (NMSS) was awarded to a partnership between a multiple sclerosis research team at the Icahn School of Medicine at Mount Sinai and Karyopharm Therapeutics Inc., a clinical stage pharmaceutical company. Dr. Patrizia Casaccia, MD, PhD, Professor in the Departments of Neuroscience and Genetics and Genomics, at Icahn School of Medicine at Mount Sinai, will be the academic lead. She will test the effectiveness of a novel Karyopharm compound that can be orally administered and aimed at stopping the progressive phase of the disease. With the 14-month grant, Dr. Casaccia also hopes to gather information that will help design future clinical trials for MS treatments.
Karyopharm specializes in the synthesis of Selective Inhibitors of Nuclear Export, also known as SINE compounds. These compounds are thought to prevent the cause of irreversible damage to neurons, by blocking the early stages of neurodegeneration. Dr. Casaccia's laboratory first identified nuclear export as an important mechanism related to the initial events occurring in neurons and eventually leading to neurodegeneration. As inhibitors, these novel compounds target the nucleus in neurons, and block the accumulation of toxic substances in the axons. Axons are coated with myelin, and they can be damaged because myelin is destroyed or because they can be directly attacked by toxic factors that accumulate during the MS disease process. Neurodegenerative symptoms result from loss of myelin. Electrical signals are transmitted from the cell body of the neuron down an axon to other nerve cells, muscles, and other cells. Signal transmission slows down and progressive disability results from damage to the axons and loss of neurons, due to neurodegeneration.
Dr. Casaccia underscored the new strategy in MS drug development. "What's unique about this work is that SINE compounds target and prevent nuclear export, which is critically important for the neurodegenerative phase of the disease," she said. Preliminary experiments in Dr. Casaccia's laboratory have been encouraging. In mouse models, oral administration of the new compound to mice with paralysis of the tail and hindlimb, allowed them to walk again.
"The idea of rebuilding the nervous system and protecting it from ongoing MS damage was just a dream a few years ago," said Timothy Coetzee, Chief Advocacy, Services and Research Officer at the National MS Society. "Now, because of efforts by the research community as well as focused investments by the Society, we can see a future where people with MS will have treatments that could restore what's been lost."
In partnering with Karyopharm Therapeutics Inc., Dr. Casaccia will test these oral compounds in preclinical models and unravel their mechanism of action. The work would not be possible if the National MS Society did not invest $500,000 with Karyopharm through Fast Forward, as part of a comprehensive approach to MS research and treatment focusing on accelerating commercial development of promising research discoveries.
"We look forward to collaborating with Dr. Casaccia, who has dedicated herself to advancing research in multiple sclerosis and other important diseases," said Karyopharm Founder, Chief Scientific Officer, and President of Research and Development, Sharon Shacham, PhD, MBA.
Fred Lublin, MD, Saunders Family Professor of Neurology and the Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center also applauded this research. "Developing novel approaches to treating the neurodegenerative component of MS is critically important for our efforts at halting this disease and then reversing the damage. Existing medications for MS only aim to reduce the number of relapses. They are not restorative to the nervous system."
Source: The Mount Sinai Hospital (22/11/13)
Multiple sclerosis (MS) is a disease of uncertain etiology characterized by demyelinating lesions affecting the central nervous system. In 2009, Dr. Paolo Zamboni et al described an association between MS and extra cranial venous outflow restrictive lesions detected by extra cranial and intracranial venous duplex studies.
They named this venous outflow restriction chronic cerebrospinal venous insufficiency (CCSVI). In addition, they introduced an endovascular interventional treatment for CCSVI in an open-label study that included 65 MS patients with post procedure follow-up of over 18 months. Several subsequent prospective open-label, non-randomized studies investigated safety and efficacy of venous angioplasty in MS. Findings from these studies have generated considerable controversy but remain unproven.
Since 2009, over 30,000 MS patients worldwide have undergone an endovascular procedure. The vast majority of these procedures were done outside a clinical trial raising skepticism.
Dr. Robert Zivadinov, Professor of Neurology, Department of Neurology State University of New York at Buffalo (Buffalo, NY) reported, “The objective of our study, The Prospective Randomized Endovascular Therapy in MS (PREMiSe), was to investigate the safety and efficacy of percutaneous transluminal venous angioplasty (PTVA) for correcting CCSVI in MS in the setting of a prospective, double-blind, sham-controlled, randomized pilot trial.”
PREMiSe is believed to be the first prospective randomized double-blinded, controlled study of balloon angioplasty for MS performed with Institutional Review Board approval in a rigorous fashion in the U.S. with significant safeguards in place to ensure careful determination of risks and benefits. All screening, diagnostic, interventional and follow-up procedures and visits were performed at no cost to the patients.
"The study’s key findings are that while the treatment is safe and was not associated with serious adverse events, it did not provide sustained improvement in MS patients,” explained Zivadinov.
The trial enrolled 30 MS patients. Phase 1 was a safety trial, involving 10 MS patients and Phase II involved a total of 20 MS patients, who were randomized to receive treatment or placebo. Researchers found no difference in clinical symptoms, brain lesions as determined on MRIs or quality of life outcomes between MS patients who underwent balloon angioplasty to correct CCSVI and those who did not receive the treatment.
Zivadinov said, “Based on our findings, our primary message to MS patients and their doctors is that endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) should only be done in the context of randomized, double-blinded, controlled studies like PREMiSe.
About VEITHsymposium: Now in its fourth decade, VEITHsymposium provides vascular surgeons, interventional radiologists, interventional cardiologists and other vascular specialists with a unique and exciting format to learn the most current information about what is new and important in the treatment of vascular disease.
Source: PR Web ©Copyright 1997-2013, Vocus PRW Holdings, LLC (22/11/13)
Mapi pharma patents new MS drug(22/11/13)
Once-a-month treatment for multiple sclerosis gains US patent – inching Israeli pharma company closer to the market.
Only three years after going into business in Ness Ziona, Israel, Mapi Pharma has won a US patent for a promising drug in its pipeline – a slow-release form of glatiramer acetate for treating multiple sclerosis (MS) symptoms just once a month.
“We believe in two to three years they could be in the final stage of development, and about three years to market,” says Mapi Pharma president and CEO Ehud Marom.
Informed by his background at Teva Pharmaceuticals, where he headed global operations for innovative drugs including Copaxone; at Peptor, where he led development of diabetes drug DiaPep; and at Gamida Cell, Makhteshim-Agan and Pharma Two B, Marom came to Mapi knowing exactly what he wanted to focus on.
“We started mainly at ‘eye level’ with technologies to improve patients’ quality of life,” he tells ISRAEL21c.
“For MS, we chose to do something to improve the life of the patient by developing a technology that can be injected once a month instead of daily.”
Mapi’s glatiramer acetate product uses the same active therapeutic agent as the currently used drug, just in a novel form.
“The idea is to let the active material release slowly — and not as it is done today, immediately — by coating the active material with polymers. This provides a better quality of life, it’s safer and more convenient, and improves compliance and efficacy,” says Marom. “The FDA is supporting this way of delivering drugs for people with chronic diseases.”
MS is a chronic, often disabling disease that attacks the central nervous system. Unpredictable symptoms include numbness in the limbs, paralysis and loss of vision. The global market for MS pharmaceuticals is estimated to be approximately $10 billion.
Clinical trials for efficacy are set to start in January in Israel, and then in European and US centers. “There is a high chance that the efficacy will be the same because we changed the formulation, not the active molecules,” he points out.
Source: ISRAEL21C © 2013 ISRAEL21C (22/11/13)
Genzyme, a Sanofi company, announced today that Health Canada has approved Aubagio® (teriflunomide) 14 mg as monotherapy for the treatment of patients with relapsing remitting multiple sclerosis (RRMS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.
"There are many patients who simply cannot tolerate injections and have had no simple, effective, once daily oral medication until now," said Dr. Mark Freedman, Director, Multiple Sclerosis Research Unit and Professor of Neurology and Senior Scientist at the University of Ottawa and Ottawa Hospital Research Institute. "As a new oral treatment option, Aubagio is an important advancement for the MS community and may help improve quality of life for people living with this debilitating disease."
The Health Canada approval was based on efficacy data from two Phase III clinical trials - TEMSO (TEriflunomide Multiple Sclerosis Oral) and TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis). In the TEMSO trial, Aubagio 14 mg significantly reduced the annualized relapse rate (p=0.0005) and the time to disability progression (p=0.0279) at two years versus placebo in patients with RRMS. In the TOWER trial, Aubagio 14 mg significantly reduced the annualized relapse rate (p=0.0001) and the time to disability progression sustained for 12 weeks (p = 0.0442) was statistically significantly reduced versus placebo in patients with RRMS.
"MS impacts each person differently, which is why increased options are important when it comes to making personal treatment decisions. The more treatment options that are available the more choices Canadians living with MS have to potentially improve their overall quality of life," said Dr. Karen Lee, Vice-President, Research, Multiple Sclerosis Society of Canada. "As we learn more about MS and develop therapies that reduce the frequency and severity of relapses in relapsing-remitting MS, we hope that we'll also uncover treatments for people whose disease is steadily progressing."
New positive data from the TOPIC study of Aubagio was presented at the 29th Congress of the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark. The double-blind, multi-centre trial enrolled 618 patients who had experienced a first acute or sub-acute, well-defined neurological event consistent with demyelination as well as onset of MS symptoms within 90 days of randomization, and MRI scan showing two or more lesions characteristic of MS. The two-year study was designed to assess whether early initiation of Aubagio in patients who experienced their first neurological symptoms suggestive of MS could prevent or delay a second clinical attack.
The TOPIC study found Aubagio 14 mg significantly reduced the risk of a new clinical relapse over the two-year study period. There was a 35 per cent reduction among patients who received AUBAGIO 14 mg compared to placebo (p=0.0374).
"We are very excited that Aubagio will be available for Canadians living with RRMS," said Peter Brenders, General Manager, Genzyme Canada. "Health Canada's approval of our first MS therapy represents an important milestone for us, and we are proud of our commitment to long-term leadership and partnership with the MS community."
As part of its commitment to MS patients, Genzyme has developed the MS One to One™ program. MS One to One will offer comprehensive support services, including: reimbursement navigation and other financial assistance, patient education and compliance services, medication delivery, and facilitation of the accelerated elimination procedure. Staffed by dedicated MS nurses and highly trained representatives, MS One to One can provide support for individuals living with MS, their health care providers, family and loved ones. Please consult your healthcare provider for more information.
In MS clinical studies with Aubagio, the incidence of serious adverse events were similar among Aubagio and placebo-treated patients. The most common adverse events associated with Aubagio in MS patients included alopecia, diarrhea, increased ALT levels, headache and nausea.
The Aubagio label includes a boxed warning citing the risk of hepatotoxicity and teratogenicity (based on animal data).
The labeling for Aubagio was also informed by the estimated 2.1 million years of patient exposure globally since the launch of leflunomide, which is indicated in the US for the treatment of rheumatoid arthritis. Teriflunomide is the principal active metabolite of leflunomide. Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide.
Aubagio is also approved in the United States, Europe, Australia, Argentina, Chile, South Korea and Mexico for the treatment of relapsing forms of MS. Marketing applications for Aubagio are also under review by additional regulatory authorities globally.
Source: Genzyme (20/11/13)
Rutgers professor’s advanced analysis could let therapy start earlier and lead MS research in new directions.
The search for the cause of multiple sclerosis, a debilitating disease that affects up to two and a half million people worldwide, has confounded researchers and medical professionals for generations. But Steven Schutzer, a physician and scientist at Rutgers New Jersey Medical School, has now found an important clue why progress has been slow – it appears that most research on the origins of MS has focused on the wrong part of the brain.
Look more to the gray matter, the new findings published in the journal PLOS ONE suggest, and less to the white. That change of approach could give physicians effective tools to treat MS far earlier than ever before.
Until recently, most MS research has focused on the brain’s white matter, which contains the nerve fibers. And for good reason: Symptoms of the disease, which include muscle weakness and vision loss, occur when there is deterioration of a fatty substance called myelin, which coats nerves contained in the white matter and acts as insulation for them. When myelin in the brain is degraded, apparently by the body’s own immune system, and the nerve fiber is exposed, transmission of nerve impulses can be slowed or interrupted. So when patients’ symptoms flare up, the white matter is where the action in the brain appears to be.
But Schutzer attacked the problem from a different direction. He is one of the first scientists to analyze patients’ cerebrospinal fluid (CSF) by taking full advantage of a combination of technologies called proteomics and high-resolution mass spectrometry. “Proteins present in the clear liquid that bathes the central nervous system can be a window to physical changes that accompany neurological disease,” says Schutzer, “and the latest mass spectrometry techniques allow us to see them as never before.” In this study, he used that novel approach to compare the cerebrospinal fluid of newly diagnosed MS patients with that of longer term patients, as well as fluid taken from people with no signs of neurological disease.
What Schutzer found startled one of his co-investigators, Patricia K. Coyle of Stony Brook University in New York, one of the leading MS clinicians and researchers in the country. The proteins in the CSF of the new MS patients suggested physiological disruptions not only in the white matter of the brain where the myelin damage eventually shows up. They also pointed to substantial disruptions in the gray matter, a different part of the brain that contains the axons and dendrites and synapses that transfer signals between nerves.
Several scientists had in fact hypothesized that there might be gray matter involvement in early MS, but the technology needed to test their theories did not yet exist. Schutzer’s analysis, which Coyle calls “exquisitely sensitive,” provides the solid physical evidence for the very first time. It includes a finding that nine specific proteins associated with gray matter were far more abundant in patients who had just suffered their first attack than in longer term MS patients or in the healthy controls. “This evidence indicates gray matter may be the critical initial target in MS rather than white matter,” says Coyle. “We may have been looking in the wrong area.”
According to Coyle, that realization presents exciting possibilities. One, she says, is that patients who suffer attacks that appear related to MS could have their cerebrospinal fluid tested quickly. If proteins that point to early MS are found, helpful therapy could begin at once, before the disease can progress further.
Coyle says Schutzer’s findings may also lead one day to more effective treatments for MS with far fewer side effects. Without specific knowledge of what causes multiple sclerosis, patients now need to take medications that can broadly weaken their immune systems. These drugs slow the body’s destruction of myelin in the brain, but also degrade the immune system’s ability to keep the body healthy in other ways. By suggesting an exciting new direction for MS research, Schutzer and his team may have set the stage for more targeted treatments that attack MS while preserving other important immune functions.
Schutzer sees an even broader future for the work he is now doing. He also has used advanced analysis of cerebrospinal fluid to identify physical markers for neurological ailments that include Lyme disease, in which he has been a world leader in research for many years, as well as chronic fatigue syndrome. He says, “When techniques are refined, more medical conditions are examined, and costs per patient come down, one day there could be a broad panel of tests through which patients and their doctors can get early evidence of a variety of disorders, and use that knowledge to treat them both more quickly and far more effectively than is possible now.”
This research was funded by the National Institutes of Health.
Source: Newsfix.ca Copyright 2013 NewsFix.ca (20/11/13)
A team of Ottawa doctors is preparing to publish a full report on its breakthrough multiple sclerosis treatment study that has so far eliminated the disease in those treated.
The experimental study began about 13 years ago as a last resort for patients who fail to improve on drug therapy and who suffer severe symptoms of MS. Snippets of the results have been published “here and there,” said, neurologist Dr. Mark Freedman, one of the leads of the program at The Ottawa Hospital, but its never been published in its entirety.
No specific date has been set for its release, but the team’s findings are far from secret. With MS not returning in any of the 24 participants, patient success stories appear in news media across the country. Since the original study’s completion, about another dozen patients have been treated with all of them showing the same results.
Eliminating MS completely and watching patients improve surprised both Freedman and Dr. Harold Atkins, a bone-marrow transplant expert, who started the study. The two originally set out to monitor the development of the disease and find a way to treat it. Their theory was this: Wipe out the entire immune system, reboot it with a transplant of the patient’s own bone marrow and wait for MS to regenerate.
“We thought we might be able to intercept one of the signals that initiates the disease and that would then give us a clue on how to treat it,” Freedman said. He jokes that they “had, in effect, failed because the disease never came back. No one expected to see zero disease activity after the transplant.”
Patients from Vancouver to Newfoundland, who had given up hope, became part of the original 24, including third-year medical student Alex Normandin from Montreal.
The aspiring doctor noticed alarming symptoms of fatigue, numbness and problems with balance and co-ordination. Researchers at the Montreal Neurological Institute confirmed he has a particularly aggressive form of MS, an unpredictable and degenerative disease that affects the central nervous system.
Most patients do not become severely disabled because the illness moves slowly. But in Normandin’s case, the destruction was so fast that doctors expected him to need a wheelchair within months.
Normandin, however, learned of the cutting-edge treatment run by Freedman and Atkins. He became patient No. 19 in the experiment and had his transplant in Ottawa in December 2008.
The procedure has its risks. One patient died in an earlier phase of the trial. It was in 2001 or 2002, Freedman recalled, saying the death was due to the pill form of the drug Busulphan. Used early on in the experiment, the drug attacks the liver twice, both when it enters the body and again when it leaves. But within a year, the team had found that a new intravenous version of the drug improved patient safety tremendously.
Freedman had the task of trying to scare patients by telling them the risks.
“My job was to talk everybody out of it,” he said. “It really is the hardest thing they’ll have to do in their lives. It is a bit of a gamble, but with the fantastic team we have in Ottawa, it’s less of a gamble.”
All participants showed dramatic improvement, and none reported relapses, according to a study on the Freedman-Atkins treatment by a team of MS researchers at the Neuro and the Université de Montréal.
Plus, magnetic resonance imaging (MRI) showed no new lesions in the brain, “no new MS disease activity,” according to findings published in the latest issue of Annals of Neurology.
For Normandin, he’s now a family physician in private practice on the West Island and no longer takes medication for the illness. His fatigue and balance problems continue to diminish daily.
But despite such dramatic results, none of the MS researchers in this study is calling the procedure a cure.
For one thing, it is not known whether the treatment is good at stopping other kinds of MS, explained neurologist Amit Bar-Or of the Montreal Neurological Institute and McGill University and the study’s principal investigator.
Also, bone-marrow stem-cell transplants to treat MS are not approved outside of clinical trials because while the disease itself is not deadly, the procedure is fatal in as much as five per cent of patients.
But Freedman questions the risk rate. He says the five-per-cent figure was from data collected in the 1990s as the team prepared for the experiment. That number has since dropped to about one per cent, he said.
In addition to medical advancements, by comparing the immune responses in patients before and after the treatment, researchers discovered a key biological target for new therapies that might be able to provide similar benefits without the risks associated with knocking out someone’s immune system to facilitate a bone-marrow transplant.
Several studies have already noted that in MS patients, the body’s immune system attacks its own cells. Overactive T cells (a type of white blood cells called lymphocytes) — that are responsible for defending the body against bacteria, viruses and other parasites — can also damage myelin, the protective insulation covering nerves.
The concept is straightforward, Bar-Or explained. To fight an infection, different types of T cells mount a quick response, then other T cells quickly ratchet back that response, he said. But in auto-immune conditions, including MS, this regulation goes awry and the body attacks itself.
Researchers have zeroed in on a particular subset of T cells, called TH17 cells, that have a substantially diminished function following the experimental transplant. The discovery could help researchers target treatment in MS patients generally.
“We are cautious in not claiming we have figured out all cells responsible for all relapses in all MS patients,” Bar-Or noted. “Keep in mind these patients have very aggressive MS, so maybe TH17 are particularly important in these patients.”
Emerging treatments, however, are already attempting to target TH17 cells, but the story is even more complicated, Bar-Or said.
“We don’t know everything about them (TH17 cells) even in terms of basic immunology. It’s likely that within the TH17 subset there may be particular bad guys ... It would be nice to know which because we need to have these cells some of the time. Getting rid of all of them all of the time, may not be completely safe.”
Both the clinical study at the Ottawa Hospital Multiple Sclerosis Research Unit and biological study in Montreal were funded by the Research Foundation of the Multiple Sclerosis Society of Canada.
Canada has one of the highest rates of MS in the world — affecting about 55,000 to 75,000 people.
Normandin says his illness has been a blessing in disguise, giving him a unique perspective not found in medical text books.
“It changed my whole outlook on life. It definitely affects the way I see patients. I’m more sensitive in how to talk to them and more empathetic dealing with chronic diseases.”
He was once on a career track where the focus was work, but now “life balance” is everything and he is grateful for the treatment that gave him his life back and allowed him to work in a clinic where he can spend as much time as necessary talking to patients.
“Life is great,” he said. “I love to say it.”
Source: The Ottawa Citizen © Copyright (c) The Ottawa Citizen 2013 (18/11/13)
Testosterone treatment was associated with reversal of gray matter atrophy in a population of men with multiple sclerosis (MS), researchers reported here.
In a small pilot study of male multiple sclerosis patients, treatment with 100 mg of testosterone was associated with diminished atrophy of gray matter over a 6-month window and reversal to pre-study levels with significant increase in the right middle frontal gyrus after 12 months of therapy, according to Florian Kurth, MD, of the University of California Los Angeles, and colleagues.
However, there was no association with lesion volume or newly occurring lesions with testosterone treatment, Kurth said during an oral presentation at the Society for Neuroscience meeting.
Kurth also acknowledged the risks of myocardial infarction associated with testosterone therapy, but noted that treatment should be delivered on a patient-by-patient basis that should not overshadow the need for further randomized, controlled trials with larger populations to study this association, adding that the differences from therapy were "not merely cosmetic."
Kurth and his colleagues conducted a pilot clinical trial to study the effect of testosterone on cerebral gray matter in 10 men with relapsing-remitting MS, having noted that gray matter atrophy "correlates better with disability than [white matter] lesions do" in multiple sclerosis.
They also noted that past research has shown that testosterone has neuroprotective properties in men.
Current MS treatments predominantly affect relapse and white matter lesions.
Participants were 29 to 61 and had not received disease-modifying treatment. Over the 18 months of the study, they underwent voxel-based morphometry in MRI scans at baseline, month 6, month 12, and month 18 to measure changes in gray matter volume.
During the initial 6 months, there was an observation phase during which participants received no treatment. Over the next 6 months, they underwent a "wash-in" period where they were observed for efficacy of treatment. The final 6 months was the "treatment phase" during which it was expected that the full effects of testosterone treatment would be visible on brain scans.
Over the observation period, there was a significant widespread decrease in gray matter. This loss was strongly tempered during the wash-in period, and gray matter volume had returned to baseline levels after 12 months of treatment.
Kurth and colleagues noted that the testosterone treatment did not significantly effect the overall lesion volume or the number of new lesions.
They concluded that these outcomes showed that testosterone may serve as a complementary treatment to current MS therapies, which prevent inflammation and white matter lesions.
The study was supported by NIH and MNSS grants.
The authors declared that they had no conflicts of interest.
Primary source: Society for Neuroscience
Source reference: Kurth F, et al "Testosterone treatment increases regional gray matter in men with multiple sclerosis" SFN 2013; Abstract 792.01.
Source: MedPage Today © 2013 MedPage Today, LLC (18/11/13)
Pharmaceutical Industries Ltd.’s Copaxone multiple-sclerosis drug to generic competition in May.
The lower court ruling invalidated one of the company’s patents and shaved more than a year off the legal protection for Copaxone, a treatment that generated $2.25 billion in U.S. sales for Teva in 2011. Chief Justice John Roberts today rejected Teva’s request to put that ruling on hold while the court decides whether to take up Teva’s appeal.
The rebuff is a victory for the generic-drug makers challenging the Teva patents. Those include Momenta Pharmaceuticals Inc, which is developing a generic version with Novartis AG’s Sandoz, and Mylan Inc, which has said it expects to be on the market in May.
Teva, based in Petach Tikva, Israel, said in court papers that it would suffer “irreparable injury” if the lower court ruling remained in effect. Even if the court were to take up the company’s appeal, review wouldn’t take place until the nine-month term that starts in October 2014, Teva said.
“Because the key Teva patent that the Federal Circuit invalidated will expire in September 2015, proceedings on the merits in this court could easily consume most of the remaining life of the patent,” the company argued.
The generic-drug companies said the case would have been eligible for the court’s current calendar had Teva moved more quickly after the July 26 appeals court decision.
Competition “would greatly benefit multiple-sclerosis patients, who pay about $40,000 per year for Copaxone,” the companies argued.
Multiple sclerosis causes the immune system to attack the insulating tissue around nerve fibers. It stops nerve cells from sending signals, sapping patients’ energy, blurring their vision and slowly depriving them of mobility, balance and coordination. Copaxone is an injection designed to work with the body’s immune system to cut relapses of the disease.
The case is Teva v. Sandoz, 13A458.
Source: Bloomberg ©2013 BLOOMBERG L.P (14/11/13)
Lemtrada hasn’t proven to help against disability in the treatment of relapsing multiple sclerosis, said U.S. advisers who questioned whether the company’s studies were conducted well enough to assess the drug.
While the U.S. Food and Drug Administration advisory panel decided that potential safety risks don’t preclude approval of Lemtrada, its members voted 14-2 that the drug didn’t help improve a patient’s disability. The agency isn’t required to accept the recommendations of its advisers.
Lemtrada, approved in the Europe Union in September, was a key part of Paris-based Sanofi’s $20 billion acquisition of Genzyme Corp. in 2011. If cleared in the U.S., the drug would enter a crowded field in which relapsing MS patients now have 10 treatment options with varying degrees of efficacy, including Biogen Idec Inc.’s Tecfidera and Teva Pharmaceutical Industries Ltd.’s Copaxone.
“If the study is biased, then everything that flows from the study can’t be trusted,” Robert Clancy, a panel member and professor of neurology and pediatrics at the University of Pennsylvania School of Medicine, said at yesterday’s meeting. The panel voted 11-6, with one abstention, that the two large studies Sanofi submitted on the drug’s behalf weren’t adequate and well-controlled.
The FDA is expected to decide whether to approve Lemtrada by Dec. 27. The agency will probably issue a so-called complete response letter that rejects the drug until the company does further work, said Jeffrey Holford, an analyst at Jefferies in New York.
“With the panel voting that the studies were not adequate and well-controlled, the FDA probably has to issue a CRL,” Holford wrote in a note today. “We continue to see the probability of approval at 20 percent to 30 percent.”
Lemtrada may generate sales of $672 million in 2017, according to the average of eight analysts’ estimates compiled by Bloomberg. Bayer AG plans to co-promote the drug and will receive payments based on sales.
Multiple sclerosis is a debilitating disease that attacks the central nervous system. Relapses, or flare ups, are episodes of worsening neurological function, according to the National MS Society.
Several patients who said they had severe MS testified today in favour of Lemtrada’s approval, imploring panel members to leave the weighing of risk versus benefit to those who have the disease and their physicians.
“It’s critical that people with significant disease who stand to lose function and become disabled have the opportunity to access this drug,” said David Goldblatt, a neuroradiologist from Austin, Texas, who said he started taking Lemtrada 10 years ago.
“I understand your issues with safety,” Goldblatt told the panel. “I think that nowadays patients are taking more responsibility and should be allowed to make the decision that they may decide that the risk/benefit ratio is adequate for them, that they would like to take this medication.”
The panel agreed, with many members saying they voted that the drug’s safety issues didn’t preclude its approval because patients should be allowed to make that decision with their doctor. While panelists said the drug appeared to be effective against the disease, they also voted unanimously that Lemtrada shouldn’t be a first option for patients, if approved.
“For the foreseeable future, I would rank it as a third-line drug,” said Justin Zivin, a panel member and professor emeritus at the University of California at San Diego.
FDA staff determined in a Nov. 8 report that Sanofi’s annual infusion has “serious and potentially fatal safety issues” including risk of cancer and autoimmune and thyroid diseases. FDA staff also questioned Sanofi’s claims the drug is effective.
The company’s decision not to keep secret which patients in clinical research were taking the medicine or an older treatment and the subjective nature of determining whether the drug was working may have skewed results, agency staff said. That was a main focus of yesterday’s FDA advisory panel discussions.
Sanofi said it was unable to keep that information confidential because of the differences in how the drugs, Lemtrada and an older treatment, were given, including annual dosing compared with three times a week. Follow-up data showed findings consistent with clinical trial results, Sanofi said in an e-mailed statement on Nov. 8.
“We are pleased that the advisory committee clearly recognized the effectiveness of Lemtrada and voted unanimously that the safety profile should not stand in the way of approval,” Jack Cox, a spokesman, said in an e-mailed statement today. “The committee vote did acknowledge FDA’s concerns around study design but this appears not to have had an impact on the committee’s votes of the effectiveness and safety profile of Lemtrada. We will work with the agency to support their completion of the review process.”
Lemtrada won European Union approval in September and the active ingredient alemtuzumab was cleared by the FDA in 2001 to treat a certain form of leukemia, though the drug is no longer for sale.
Other treatments for relapsing MS include another Sanofi drug Aubagio, Biogen’s Tecfidera and Tysabri and Teva’s Copaxone. Lemtrada is given through two courses of infusions given a year apart.
Source: Bloomberg ©2013 BLOOMBERG L.P. (14/11/13)
A protein found in HDL, or ''good,'' cholesterol may help protect against the effects of multiple sclerosis, according to new research.
In the study, patients with MS had much lower levels of the protein than did healthy people, says study researcher Lidia Gardner, PhD. She is an assistant professor of neurology at the University of Tennessee Health Science Center.
Those with more severe forms of MS, known as progressive, had even lower levels of the protein than those with a 'milder' form called relapsing-remitting. The protein is known as ApoA1.
ApoA1 is the main component of HDL. It is known to protect the body from inflammation.
In MS patients, inflammation occurs when the body's immune system attacks cells of the brain, spinal cord, and optic nerve.
Gardner presented the findings at the Society for Neuroscience's annual meeting in San Diego.
"I think it's an interesting preliminary study that has potential [applications] for people living with MS,'' says Bruce Bebo, PhD. He is associate vice president of discovery research for the National Multiple Sclerosis Society. He was not involved in the study.
Comparing Protein Levels in Patients
Gardner and her team took blood samples from four groups. They included a group without MS and a group for each of the three forms of MS.
Compared to those without MS, all the MS patients had lower levels of the cholesterol protein. This was true no matter what type of MS they had. It was reduced by 25% in people with relapsing remitting MS, 50% in people with secondary progressive MS, and 75% in people with primary progressive MS.
"I think you have to take the findings with some caution, because they are very preliminary," Bebo says.
Other research has looked at prescribing cholesterol-lowering drugs, known as statins, to increase good cholesterol in MS patients. The studies have produced conflicting findings, Gardner says.
She plans to focus next on the process of making and then increasing ApoA1 to help.
For now, lifestyle changes such as eating a vegetarian, vegan, or low-fat diet may help boost levels of the cholesterol protein, Gardner says. Exercise may also help.
Source: WebMD ©2005-2013 WebMD, LLC (13/11/13)
A protein involved in blood clotting may be a new indicator to help detect multiple sclerosis (MS) lesions before symptoms arise. The presence of the clotting protein, thrombin, signals an early stage of the disease when the blood-brain barrier is breached and the brain’s immune response is set into motion. The research was presented at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.
30,000 scientists are attending this meeting.
“Our research shows this indicator is a promising approach for detecting MS-like lesions early, even before major symptoms appear,” said senior author Katerina Akassoglou, Ph.D., of the Gladstone Institutes and the University of California, San Francisco. “Such sensitive indicators could act as red flags that signal neuroinflammatory changes in the brain not only in MS, but also in other diseases such as Alzheimer’s.”
MS is a debilitating disorder that can be intermittent or progressive, and causes numbness, fatigue, difficulty walking, paralysis, and loss of vision in 2 million people worldwide. MS arises when the body’s immune system attacks its own myelin sheaths, the protective coverings that surround neurons and allow signals to move from one cell to the next.
The researchers found that thrombin, usually a beneficial protein involved in blood clotting, builds up in the central nervous system as MS progresses. Thrombin enters in the brain together with fibrinogen, another clotting protein when the protective barrier between the blood and brain becomes leaky. Thrombin converts the fibrinogen to fibrin which activates brain’s immune cells that break down the protective myelin sheath that surrounds neurons in the central nervous system. Because thrombin levels increase as the disease progresses, the researchers conclude that it could be used as an early detector of the disease.
In their studies, the researchers used a mouse model and demonstrated that MS symptoms increased as thrombin levels rose. Early detection of MS could result in more successful treatment of the disease.
Research was supported with funds from the National Multiple Sclerosis Society, the Nancy Davis Foundation for Multiple Sclerosis, and the National Institutes of Health. Dr. Akassoglou outlined her findings in a press conference held on Sunday, November 10, and this summary was distributed with the press release. The scientific presentation of Dr. Akassoglou’s work will be delivered on Monday, Novermber 11.
Source: Bioquick News (11/11/13)
Revalesio Corporation has announced a new collaboration with noted neurologist Dr. Roland Martin, Head of Neuroimmunology and MS Research at the Department of Neurology, University Hospital Zurich. Dr. Martin will be conducting a Phase IIa clinical trial of RNS60 in patients with relapsing-remitting multiple sclerosis (RRMS or MS). With 30 years experience, Dr. Martin is a recognized leader in the field of neuroimmunology and multiple sclerosis research.
The study will compare measurements of disease activity and progression in patients with RRMS during 6-months treatment with RNS60. The open label study will enroll 15 patients and evaluate the use of RNS60 by intravenous administration compared to patient's pre-treatment disease activity. The main outcome of the study will be the reduction of inflammatory activity in the brain as measured by Gd contrast-enhacing MRI lesions. Additional measures include progression of disability and biomarkers for RNS60 and general inflammation. The study will be conducted at the University Hospital Zurich in Switzerland and at Innsbruck Medical University in Innsbruck, Austria.
"Our MS development work with RNS60 has been an extraordinary process of discovery and pioneering research," said Dr. Richard Watson, Revalesio's Chief Science Officer. "We have published much of our data regarding RNS60's mechanisms in the pre-clinical models and are pleased to have Dr. Martin as a collaborator and to see RNS60 advance into the clinic for MS. We are hopeful this study will provide an efficacy signal that demonstrates RNS60's therapeutic potential and informs future clinical research."
RNS60 has been tested in numerous pre-clinical models of MS and has shown the ability to halt disease progression by limiting glial infiltration (inflammation in the brain), protecting myelin and enriching the regulatory T-cell (TREG) populations in animals treated with RNS60. Data from these pre-clinical models can be found in the academic journal PLOS ONE.
About RNS60 Revalesio has pioneered the use of RNS60 as a therapeutic that alters whole cell conductance through effects on voltage-sensing membrane-bound proteins, thereby modulating the activity of G protein-coupled receptors and the secretion of cytokines, chemokines resulting in decreased inflammation and cell death. RNS60 contains charge-stabilized nanostructures (CSN) that are created by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow. RNS60 has demonstrated a reduction in inflammatory responses that are linked to numerous diseases, including neurodegenerative, respiratory and cardiovascular diseases.
Source: The Sacramento Bee Copyright © The Sacramento Bee 2013 (11/11/13)
Research reveals new understanding, warning signs, and potential treatments for multiple sclerosis(11/11/13)
Scientists are gaining a new level of understanding of multiple sclerosis (MS) that may lead to new treatments and approaches to controlling the chronic disease, according to new research released today at Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.
MS is a severe, often crippling, autoimmune disease caused by the body's immune system attacking the nervous system. Today, more than two million people worldwide suffer from MS and other neuroinflammatory diseases. MS usually strikes in early adulthood and manifests with symptoms including vision loss, paralysis, numbness, and fatigue. The disease can be intermittent or progressive and currently has no cure.
Today's new findings show that:
Scientists are one step closer to understanding how antibodies in the blood stream break past the brain's protective barrier to attack the optic nerves, spinal cord, and brain, causing the symptoms of neuromyelitis optica, a rare disease similar to MS. Understanding how the antibodies bypass the protective blood-brain barrier could provide new approaches to treating the disease. (Yukio Takeshita, MD, PhD, abstract 404.09).
A protein involved in blood clotting might serve as an early detection method for MS before symptoms occur. Early detection of the disease could lead to more effective early treatments (Katerina Akassoglou, PhD, abstract 404.11).
Low levels of a cholesterol protein correlate with the severity of a patient's MS in both human patients and mouse models. The finding suggests the protein, known to protect against inflammation, may protect against developing MS, and possibly even aid in the regeneration of damaged neurons. This research opens the door to cholesterol drugs as a possible new avenue for MS treatment (Lidia Gardner, PhD, abstract 404.01).
Other recent findings discussed show that:
A type of immune system cell has been found to directly target and damage nerve cell axons, a hallmark of MS. This may reveal a target for new therapies (Brian Sauer, PhD, presentation 404.06).
While no treatments to rebuild cells damaged by MS currently exist, scientists have found that when exosomes—tiny, naturally occurring "nanovesicles"—are produced by dendritic cells and applied to the brain, they can deliver a mixture of proteins and RNAs that promote regeneration of protective myelin sheaths and guard against MS symptoms (Richard Kraig, MD, PhD, presentation 812.02).
"The findings shown today represent real promise for the millions suffering from MS," said press conference moderator Jeffrey Rothstein of Johns Hopkins University and an expert in neurodegenerative diseases. "These studies are breakthroughs in understanding and treating a disease that remains uncured, difficult to diagnose, and for which it is very difficult to prevent progression."
Source: MedicalXpress © Medical Xpress 2011-2013, Phys.org network (11/11/13)
Sanofi’s multiple sclerosis treatment Lemtrada may not offer enough benefit to patients to outweigh risks including cancer, U.S. regulators said. The French drugmaker’s shares fell.
Lemtrada’s “serious and potentially fatal safety issues,” which include the risk of autoimmune and thyroid diseases, may make the medicine too dangerous to approve unless there is substantial clinical benefit shown, Food and Drug Administration staff said in a report today. Agency reviewers also questioned whether Sanofi conducted adequate trials to prove the annual infusion works.
“That’s like a death sentence,” said Fabian Wenner, an analyst with Kepler Cheuvreux in Zurich, “It isn’t what everyone expected, an issue with the safety. It seems to be a more fundamental issue here.”
Lemtrada, approved in Europe earlier this year, was at the center of Paris-based Sanofi’s $20 billion acquisition of Genzyme Corp. in 2011. Shareholders who have contingent value rights stand to receive cash payments if Lemtrada is approved. Bayer AG (BAYN) plans to co-promote Lemtrada and will receive payments based on sales.
“The certainty of the risks of potentially lifelong hypothyroidism, serious infusion reactions, melanoma and other malignancies, Graves’s ophthalmopathy and other autoimmune disorders, and prolonged increased susceptibility to infection may not be balanced by the uncertainty that exists in the limited evidence of the potential clinical benefits from clinical trials that were not well-controlled,” FDA drug reviewer John Marler wrote in the report.
Nov. 13 Panel
An advisory panel on Nov. 13 will discuss whether to recommend the drug’s approval. The FDA is expected to decide whether to clear the medicine for treating relapsing MS patients by the end of the year.
Sanofi did submit trial evidence that showed Lemtrada had a significant benefit, though the company’s decision to not keep secret which patients were taking the medicine and the subjective nature of determining whether the therapy was working may have skewed results, Marler said.
Sanofi said it was unable to keep that information confidential because of the differences in how the drugs, Lemtrada and an older treatment, were given, including annual dosing compared with three times a week. Follow-up data showed findings consistent with clinical trial results, Sanofi said in an e-mailed statement.
“Our company is confident that Lemtrada offers an important step forward in the way physicians and patients will think about treating multiple sclerosis,” Sanofi said.
Sanofi fell less than 1 percent to 77.94 euros at 4:21 p.m. Paris time. The contingent value rights linked to the Genzyme acquisition dropped 68 percent to 65 cents in New York trading.
Genzyme stockholders had received one right entitling the owner to additional fees of as much as $14 per CVR by the end of 2020 if Sanofi met certain goals, most of them tied to the approval and sale of Lemtrada.
Lemtrada won European Union approval in September and the active ingredient alemtuzumab was cleared by the FDA in 2001 to treat a certain form of leukemia, though it is no longer for sale.
The drug may generate sales of $691 million in 2017, according to the average of eight analysts’ estimates compiled by Bloomberg.
Source: Bloomberg ©2013 BLOOMBERG L.P. (08/11/13)
Multiple sclerosis is most often found in northern Europe, north America, Australia and New Zealand, all populated by European colonists.
In Britain, the numbers affected are highest in Scotland, far higher than they are in England or Wales, while the further north one goes in Scotland the more the figures rise: 229 per 100,000 in Aberdeen, 295 in Shetland, but 402 in Orkney.
“It has been suggested that the origins can be traced back to the Vikings who colonised those parts of northern Europe where MS is most pronounced and that ‘Viking genes’ can make people particularly susceptible to multiple sclerosis,” says the MS Society in Britain.
Today, however, the society is investigating another population group: the black Caribbeans who came to Britain after the second World War and their descendants, some of whom are displaying particular troubles coping with the often-crippling condition.
The disease progressed more quickly among a group of black Caribbeans compared with a white British group. Equally, the former group was also “more likely to experience higher levels of cognitive problems”, say researchers from King’s College and King’s College Hospital in London.
Multiple sclerosis is a neurological condition that affects the central nervous system. Globally, the numbers of sufferers is put at 2.5 million. In the UK, 100,000 people are affected, living with problems with balance and mobility, sight, along with fatigue.
“In interviews, black Caribbean people also more commonly spoke of being less able to deal with feelings of unresolved loss and confusion as a result of their rapidly advancing symptoms,” the researchers say.
Memory problems are mentioned again and again. “I always used to have a very good memory, now my memory’s very, very poor. Long-term memory’s fine, but my short- term memory is really, really bad,” said one 36-year-old man.
“I could have a talk with a friend today and arrange something for tomorrow and if I haven’t written it down, it will go straight out of my head.”
For now, possible explanations are few. “The reasons for the differences were not explored in this study, but could possibly include later perceptions of symptom onset, a genetic predisposition to more severe disease or less exposure to vitamin D,” says the research.
However, it has been known for decades that first-generation black Caribbeans – the so- called “Windies” – faced a relatively low risk from MS, while their children did “not seem to have a higher risk” than those who migrated as adults.
The findings though began to change in the late 1990s. Then, a study reported that living for 20 years in Britain raised the risk, which was “broadly consistent” with a belief that environment plays a key role.
The possible reasons to explain the numbers include lower socioeconomic status, a genetic predisposition to get a worse version of MS, should it come, and evidence that some black Caribbeans with MS are diagnosed later than other sections of the population.
Then there is vitamin D, with a belief that black Caribbeans suffer more than others from the shortage of sunlight in northern climes such as Britain between November and April – even though supplements can fill some of the gaps.
If the problems are clear, the solutions are not yet evident.
“Our findings demonstrated more aggressive MS disease among black Caribbeans despite a number of them being in receipt of disease-modifying therapy,” the team says in a study that was funded by the MS Society.
“More rapid disease progression leads to marked difficulties with ambulation, physical function and distress as a result of multiple losses.” The rising figures for black Caribbean MS sufferers poses issues about culturally sensitive care for the National Health Service, just as in the same way rising dementia rates do so among the elderly Irish community in Britain.
However, a distrustful attitude from minorities in general, not just black Caribbeans, to ethnic-based research can delay the discovery of problems. And some research can be skewed from the off because it is based upon “racially-based stereotypes”.
Last year, a study published by the British Medical Journal noted the cultural differences that exist between some, but not all, white British and black Caribbeans, with the latter more inclined to blame “fate or destiny” for their illness.
Urging officialdom to remember to “be mindful” of cultural differences, researchers call for appropriate investment in multi-ethnic services.If anything, the drift in Britain is away from that, not towards it.
Source: The Irish Times © 2013 THE IRISH TIMES (08/11/13)
Objectives: Yoga has been found to be effective for addressing problems with strength, flexibility, balance, gait, anxiety, depression, and concentration. Varying degrees of these problems occur in individuals with multiple sclerosis (MS). This study examined the effects of a comprehensive, 4-month yoga program on strength, mobility, balance, respiratory function, and quality of life for individuals with MS.
Methods: Twenty four individuals with MS participated in an intensive Ananda Yoga training followed by 17 weeks of home practice.
Results: Significant improvements in functional strength, balance, and peak expiratory flow and a trend toward improvements in mental health and quality of life outcomes were detected following the intervention.
Conclusions: The results of this exploratory study suggest that yoga can have a positive impact on physical functioning and quality of life for persons with mild to moderate MS.
Salgado BC, Jones M, Ilgun S, McCord G, Loper-Powers M, van Houten P.
Department of Physical Therapy, California State University, Sacramento, CA.
Sources: Int J Yoga Therap. 2013;23(2):27-38 & Pubmed PMID: 24165521 (08/11/13)
The diseases have more than the immune system in common, sharing a genetic risk factor and connection to the Epstein Barr Virus.
Scientists at the Institute of Cancer Research (ICR) in London have discovered a genetic link between Hodgkin's lymphoma and multiple sclerosis (MS), suggesting that there may be a shared mechanism of action the triggers the two diseases.
Analyzing the genes of more than 12,000 people, the researchers found two new gene variants that increase the risk of developing Hodgkin's lymphoma significantly.
According to the study, “One of these variants is linked to a gene known as EOMES that helps develop cell-mediated immunity, and is also a known risk factor for MS. This might explain why cases of Hodgkin's lymphoma and MS are found to cluster together in families.”
What Is Hodgkin's Lymphoma?
Hodgkin's lymphoma is a cancer that starts in the white blood cells, or lymphocytes, found in the lymphatic system, which is part of the body’s immune system. Lymph nodes, lymph fluid, and lymph vessels, which transport the fluid throughout the body, all make up the lymphatic system.
Because this system runs throughout the body, Hodgkin's lymphoma can start nearly anywhere. According to the American Cancer Society (ACS), the major sites are the lymph nodes, spleen, thymus, bone marrow, and digestive tract.
Lymphocytes are also thought to play an important role in MS. Normally, lymphocytes defend the body against foreign invaders like viruses and bacteria. In MS, the lymphocytes are misdirected and attack the protective covering of the nerves in the brain and spinal cord.
In a study conducted in Denmark and published in 2004, researchers followed 11,790 patients with multiple sclerosis and 19,599 of their first-degree relatives and monitored them for the development of Hodgkin's lymphoma.
They concluded that “the observed familial clustering of multiple sclerosis and young-adult-onset Hodgkin's lymphoma is consistent with the hypothesis that the two conditions share environmental and/or constitutional etiologies.” The discovery of a genetic connection between Hodgkin's lymphoma and MS is exciting progress toward understanding both, suggesting the possibility of a mutual trigger.
EBV: A Possible Culprit?
If finding an MS trigger were a “whodunit,” the Epstein Barr virus (EBV), responsible for mononucleosis, would look like a handsome suspect. It is one of the known risk factors for developing Hodgkin's lymphoma and is commonly found in people with MS. EBV and MS appear to relapse together in those who have both.
“Epstein Barr virus is the virus that causes glandular fever (mononucleosis),” explains Cancer Research U.K. on their website. “People who have had glandular fever have an increased risk of Hodgkin's lymphoma afterwards. A study published in December 2011 estimated that almost half of the cases of Hodgkin's lymphoma in the U.K. are related to EBV infection.”
Not all people with Hodgkin's lymphoma or MS have been exposed to EBV, however, suggesting that if the virus is a trigger for either, it’s certainly not the only factor.
Researchers are working on the first human trials for a vaccine to fight EBV. Further research is needed to explore the connection between Hodgkin's lymphoma and MS.
The fact that both involve the immune system, share a genetic risk factor, and seem to cluster in families suggests that we are getting closer to solving the mysteries surrounding both diseases and are perhaps one step closer to a cure.
Source: Healthline Copyright © 2005 - 2013 Healthline Networks, Inc (07/11/13)
Disabled people win living fund case(06/11/13)
Five disabled people have succeeded in a legal challenge to the government's decision to abolish the Independent Living Fund.
The £320m ILF currently provides support enabling nearly 19,000 severely disabled people in the UK to live independent lives in the community.
The High Court ruled in April that the closure decision was lawful, but this was overturned by the Court of Appeal.
The government said it was considering whether to contest the judgement.
During the Court of Appeal hearing. the five disabled argued the High Court had gone wrong in law and there had been a lack of proper consultation by ministers over the changes.
They said that, without ILF funding and support, they would be forced into residential care or lose their ability to participate in work and everyday activities on the same basis as able-bodied people.
The scheme's average payout is £300 a week, and the government has said councils, which administer most social care, will take over funding this help.
Ministers took the decision close the fund on 18 December last year.
Court of Appeal judges Lord Justice Elias, Lord Justice Kitchin and Lord Justice McCombe allowed the challenge to the High Court's earlier ruling, quashing the original decision in favour of the government.
Lord Justice McCombe said the evidence upon which the decision had been based had not given "an adequate flavour of the responses received indicating that independent living might well be put seriously in peril for a large number of people".
The disabled applicants feared that the decision to close the fund and devolve the money to local authorities would lead to a reduction, or even loss, of that money, which had previously effectively been ring-fenced.
Welcoming the "powerful" ruling, law firms Deighton Pierce-Glynn and Scott-Moncrieff & Associates, which represented the claimants, said their clients had "feared that the loss of their ILF support would threaten their right to live with dignity, and that they could be forced into residential care or lose their ability to work and participate in everyday activities on an equal footing with other people".
The Court of Appeal decision was described as being "of major importance not just for the claimants, but for all disabled people".
Minister for Disabled People Mike Penning said: "We are very pleased the Court of Appeal upheld how we undertook our consultation on the future of the fund, and they accepted that it had been carried out properly and fairly.
"We are disappointed with certain aspects of today's decision, and we will be examining the judgement very carefully and considering the implications before deciding on the most appropriate way forward, which includes seeking leave to appeal."
The Equality and Human Rights Commission was permitted by the court to intervene in the case and made submissions on the proper application of the Equality Act and UN Convention.
The ILF was established in 1988, but the government decided in 2010 that it had become "no longer appropriate or sustainable" to keep running the scheme outside the mainstream social care system. The fund closed to new applicants soon afterwards.
Source: BBC News © British Broadcasting Corporation 2013 (06/11/13)
Not long ago, Stephen Mudgway was in terrible pain and slept most of the day, his quality of life ruined by a dreadful form of multiple sclerosis (MS).
Now, thanks to an experimental new treatment developed in New Zealand, he has energy and is able to get out and about.
"I enjoy life," he said.
Just a few months ago, Mr Mudgway, who has secondary progressive MS, was so fatigued he slept more than 20 hours a day and took six different medicines, including 40mg of codeine on some days.
Now, apart from a weekly dose of the treatment, he pops only one pill a day.
He sleeps for a restful eight hours each night. He can do his buttons, pull up his zip, watch TV, read a book and transfer himself from his wheelchair to his bed.
He has regained the co-ordination needed to steer his electric wheelchair.
"I can hold a normal conversation and meet new people," he said in a 30-minute telephone interview from his Christchurch nursing home.
The treatment, MIS416, is developed by New Zealand company Innate Immunotherapeutics, which has moved its operations to Australia for placebo-controlled trials on 100 people.
Close to a year ago, Mr Mudgway took part in a small three-month trial, which involved having the bacteria-based medication pumped into his veins once a week.
He and most the other participants experienced rapid improvements to their quality of life.
But these ended when the trial stopped, says Mr Mudgway.
"I went back to how I was. Even worse," he said.
He then waited six months for permission to carry on treatment on compassionate grounds.
There are no approved therapies for secondary progressive MS, says Dr Matthew Miles, CEO of MS Research Australia.
"MS is a complex disease. But we are now convinced there is an auto-immune component. Particularly in the early stages."
The medicine pumped into Mr Mudgway's veins uses two types of bacteria to regulate his immune system and reduce inflammation in his nervous system.
"It gives the body an opportunity to rebalance and repair," said Dr Gillian Webster, who heads the development team.
"There are two layers of benefit. One is fairly immediate, which improves the patient's quality of life. The acute pain goes, the vision improves, muscle strength improves.
"There is also a definite delay in progression."
But it is highly unlikely Mr Mudgway will regain use of his legs, she says. It is not a cure.
Source: NZCity © 2013 NZN, NZCity (05/11/13)
A new study by Kessler Foundation scientists sheds light on the mechanisms underlying cognitive fatigue in individuals with multiple sclerosis. Cognitive fatigue is fatigue resulting from mental work rather than from physical labor. Genova H et al: Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging" was published on Nov. 1 in PlosOne. This is the first study to use neuroimaging to investigate aspects of cognitive fatigue. The study was funded by grants from the National MS Society and Kessler Foundation.
The study investigated the neural correlates of cognitive fatigue in MS utilizing three neuroimaging approaches: functional magnetic resonance imaging (fMRI), which allows researchers to look at where in the brain activation is associated with a task or an experience; diffusion tensor imaging (DTI), which allows researchers to look at the health of the brain's white matter; and voxel-based morphometry (VBM), which allows researchers to investigate structural changes in the brain. These three approaches were used to examine how likely it is for an individual to report fatigue ("trait" fatigue), as well as the fatigue an individual feels in the moment ("state" fatigue). This study is the first to use neuroimaging to investigate these two, separable aspects of fatigue.
"We looked specifically at the relationship between individuals 'self-reported fatigue and objective measures of cognitive fatigue using state-of-the-art neuroimaging," explained Helen M. Genova, Ph.D., research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. "The importance of this work lies in the fact that it demonstrates that the subjective feeling of fatigue can be related to brain activation in specific brain regions. This provides us with an objective measure of fatigue, which will have incalculable value as we begin to test interventions designed to alleviate fatigue."
In Experiment 1, patients were scanned during performance of a task designed to induce cognitive fatigue. Investigators looked at the brain activation associated with "state" fatigue. In Experiment 2, DTI was used to examine where in the brain white matter damage correlated with increased "trait" fatigue in individuals with MS, as assessed by the Fatigue Severity Scale (FSS). The findings of Experiments 1 and 2 support the role of a striato-thalamic-frontal cortical system in fatigue, suggesting a "fatigue-network" in MS.
"Identifying a network of fatigue-related brain regions could reframe the current construct of cognitive fatigue and help define the pathophysiology of this multifaceted yet elusive symptom of MS," said John DeLuca, Ph.D., VP of Research & Training at Kessler Foundation. "Replication of these findings with larger sample sizes will be an important next step."
Source: Science Codex (04/11/13)
Aerobic exercise can boost memory in people with multiple sclerosis (MS) by up to 54 per cent, a new study has found.
The study led by Victoria Leavitt and James Sumowski, from Kessler Foundation, US, provides the first evidence for beneficial effects of aerobic exercise on brain and memory in individuals with MS.
Hippocampal atrophy seen in MS is linked to the memory deficits that affect approximately 50 per cent of individuals with MS, researchers said.
Despite the prevalence of this disabling symptom, there are no effective pharmacological or behavioural treatments.
"Aerobic exercise may be the first effective treatment for MS patients with memory problems," said Leavitt, research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation.
"Moreover, aerobic exercise has the advantages of being readily available, low cost, self-administered, and lacking in side effects," Leavitt said.
Researchers said no beneficial effects were seen with non-aerobic exercise.
Leavitt noted that the positive effects of aerobic exercise were specific to memory; other cognitive functions such as executive functioning and processing speed were unaffected.
The study's participants were two MS patients with memory deficits who were randomised to non-aerobic (stretching) and aerobic (stationary cycling) conditions. Baseline and follow-up measurements were recorded before and after the treatment protocol of 30-minute exercise sessions 3 times per week for 3 months.
Data were collected by high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment.
Aerobic exercise resulted in a 16.5 per cent increase in hippocampal volume, a 53.7 per cent increase in memory, and increased hippocampal resting-state functional connectivity.
Non-aerobic exercise resulted in minimal change in hippocampal volume and no changes in memory or functional connectivity.
"These findings clearly warrant large-scale clinical trials of aerobic exercise for the treatment of memory deficits in the MS population," said Sumowski, research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation.
Source: The India Express Copyright © 2013 The Indian Express ltd (04/11/13)
Canbex Therapeutics Ltd announced today that it has commenced a Phase I clinical trial to assess the safety and tolerability in humans of VSN16R, its novel, orally active lead compound aimed at treating spasticity in people with multiple sclerosis.
The first-in-man study of VSN16R will enrol a total of 72 healthy volunteers in a placebo-controlled, single ascending dose and multiple ascending dose design. The study is being carried out by Quintiles, the world’s leading clinical research organisation.
Spasticity is characterized by sudden and uncontrollable movements of limb and torso musculature, and is among the most painful, damaging and debilitating symptoms of multiple sclerosis. Current drug treatments have a high level of undesirable side effects, particularly sedation and cognitive dysfunction. Many patients cannot tolerate current treatments, and so are treated with palliative measures alone, or with drug regimes that result in poor quality of life.
“We are pleased to have advanced VSN16R to first dose in man, a significant milestone in the development of this novel product candidate,” stated the Chief Executive Officer of Canbex, Dr Jesse Schulman. “After years of highly promising preclinical research, we believe that VSN16R has the potential to become an important advance in the treatment of spasticity, a condition for which there remains a substantial unmet medical need.”
Initiation of the Phase I trial follows successful preclinical studies that have demonstrated the excellent safety, efficacy and tolerability of VSN16R.
Dr Keith Powell, Chairman of Canbex, said: “Our work with leading clinicians has pointed to the pressing need for a new agent that treats spasticity in multiple sclerosis without the debilitating side effects of the current best treatments.”
Canbex closed a £2.1m ($3.2m) funding round in April 2013, led by MS Ventures, the corporate venture capital arm of Merck KGaA, Darmstadt, Germany, and won a grant of £1.25 ($1.8m) from the UK government’s Technology Strategy Board in March 2013. Other investors in Canbex include the Wellcome Trust, the US National Multiple Sclerosis Society, University College London (UCL Business Ltd) and Esperante Ventures.
Source: B3C © B3C Group GmbH 2013 (04/11/13)
GeNeuro announced today that its GNbAC1 humanized monoclonal antibody was found to have a very good safety profile when administered to patients with relapsing and progressive forms of Multiple Sclerosis as part of a Phase 2a study. GNbaC1 is a first-in-class monoclonal antibody targeting a toxic protein of endogenous retroviral origin that has been identified as a potential key factor in the onset and development of multiple sclerosis. Enrollment of patients into a multinational Phase 2b study is expected to begin during the first half 2014.
“The safety data achieved in this Phase IIa study is excellent and supports the future development of GNbaC1 in both relapsing remitting and progressive MS,” commented François Curtin, CEO of GeNeuro. “While presenting at the recent ECTRIMS1 congress in Copenhagen last month, GeNeuro’s approach was highlighted as one of the most innovative and promising new treatments in clinical development against MS as it specifically targets a potential causal factor of the disease.”
In the completed Phase 2a clinical study including a six-month extension, conducted to establish safety and pharmacokinetics, GNbAC1 demonstrated very good safety following repeated administration at 2 mg/kg and 6 mg/kg. The repeated administrations did not affect the immune system, the TLR4 function was preserved and no signs of induction of immunogenicity were observed.
About the ENV toxic Protein and its role in Multiple Sclerosis and other pathologies
The sequencing of the human genome revealed human endogenous retroviruses (HERV) represent more than 8% of the human genome and result from the integration of exogenous retroviruses DNA during the primate evolution.
The Multiple Sclerosis associated retrovirus (MSRV) is a member of the HERV-W family and was initially isolated in cell cultures from patients affected with Multiple Sclerosis in the 90’s. MSRV is normally latent in the genome of individuals, but it can be re-activated by certain co-factors to expresses a pathogenic protein, MSRV-Env. Recent evidence has demonstrated that this ENV-protein is expressed in MS lesions from an early stage, is pro-inflammatory and inhibits remyelination.
Source: Rock Hill Herald Online Copywrite Rock Hill Herald 2013 (04/11/13)
A drug that contains a fragment of the teenage acne bacteria will be used to treat multiple sclerosis in a new Australian trial.
Almost 100 patients will be part of a trial to test the drug's effectiveness in treating the more advanced form of MS.
Results from unpublished early trials show modest improvement in symptoms of secondary progressive MS.
The CEO of biopharmaceutical company Innate Immunotherapeutics, Simon Wilkinson, said the drug was derived from propionibacterium acnes - the same bacterium that causes acne in teenagers.
Unlike other drugs that use a man-made version of the substance, MIS416 takes the bacteria and puts it through a manufacturing process that leaves behind just the microparticle required to elicit the immune reaction against MS.
The early trial found eight of 10 patients treated for 12 weeks had some improvement in their MS-related symptoms.
"We had 80 per cent of the patients show a 30 per cent or greater improvement in at least one measure of their MS clinical status or disability," Mr Wilkinson said.
Dr Matthew Miles of MS Research Australia said the disease typically began with relapsing/remitting MS, where attacks on the immune system came in waves.
More than half of those diagnosed with this first phase of MS will develop secondary progressive MS within 10 years.
Dr Miles said there were no disease-modifying treatments for this debilitating form of MS.
"We need to be concentrating on potential therapies for the secondary progressive MS," he said.
"Like all potential clinical trials it's a great opportunity and it's wonderful for people with MS that this is going on."
The company behind the drug has shifted part of its operations to Australia for the trial. It will start recruiting for the phase 2b trial next year.
Mr Wilkinson said running a clinical trial in Australia gave the company access to a larger patient cohort and it was considerably quicker and less expensive than in the US. Almost 25,000 Australians have MS, which affects the central nervous system.
Its symptoms can include difficulty walking, heat sensitivity, depression, and bowel and bladder dysfunction.
news.com.au Copyright © News Limited 2013 (04/11/13)
The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry.
Patients with incomplete data or Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis.
Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis.
The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48 362 relapses were recorded.
Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively.
The magnitude of this sex effect increased at longer disease duration and older age (P < 10-12). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis.
Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10-12). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.
Kalincik T, Vivek V, Jokubaitis V, Lechner-Scott J, Trojano M, Izquierdo G, Lugaresi A, Grand'maison F, Hupperts R, Oreja-Guevara C, Bergamaschi R, Iuliano G, Alroughani R, Van Pesch V, Amato MP, Slee M, Verheul F, Fernandez-Bolanos R, Fiol M, Spitaleri DL, Cristiano E, Gray O, Cabrera-Gomez JA, Shaygannejad V, Herbert J, Vucic S, Needham M, Petkovska-Boskova T, Sirbu CA, Duquette P, Girard M, Grammond P, Boz C, Giuliani G, Rio ME, Barnett M, Flechter S, Moore F, Singhal B, Bacile EA, Saladino ML, Shaw C, Skromne E, Poehlau D, Vella N, Spelman T, Liew D, Kilpatrick TJ, Butzkueven H.
Department of Medicine, University of Melbourne, Melbourne, Australia.
Source: Brain. 2013 Oct 18. [Epub ahead of print] & Pubmed PMID: 24142147 (01/11/13)
Kessler Foundation scientists correlated functional magnetic resonance imaging (fMRI) findings with the negative impact of outdoor temperature on cognitive functioning in multiple sclerosis (MS).
This study, "Warmer outdoor temperature is associated with task-related increased BOLD activation in patients with multiple sclerosis," released by Brain Imaging & Behavior corroborates the group's previous study that established that people with MS performed worse on processing speed and memory tasks during warmer outdoor temperatures versus during cooler outdoor temperatures. "Increased MS disease activity during warmer months is a recent discovery. Now, this work is the first report of brain activation associated with outdoor temperature in MS. This finding is novel and important for persons with MS who are shown to have worse cognition during warmer weather," said Victoria M. Leavitt, Ph.D., research scientist at Kessler Foundation and principal investigator for the study, funded by a grant from the National MS Society.
Kessler Foundation researchers previously demonstrated that patients with multiple sclerosis (MS) demonstrate worse cognition on warmer days. (Leavitt VM, Sumowski JF, Chiaravalloti N, DeLuca J. Warmer outdoor temperature is associated with worse cognitive status in multiple sclerosis. Neurology. 2012 Mar 27;78(13):964-8). The purpose of the current study was to identify the neurophysiological basis for worse cognition. "Here, we examined the neurophysiology underlying this temperature-cognition relationship, said Dr. Leavitt. "The association between task-related BOLD fMRI activation and outdoor temperature was investigated in 28 MS patients who demonstrated worse cognitive function on warmer days. In MS patients, warmer outdoor temperature was associated with greater BOLD activation during performance of a simple sustained attention task. The brain areas that showed greater activation on warmer days were regions typically activated by MS patients during task performance: the frontal, dorsolateral, prefrontal and parietal cortex. The relationship between outdoor temperature and cerebral activation was absent in healthy controls. Increased brain activation required by MS patients on warmer days to perform a simple task may signify neural inefficiency."
According to Dr. Sumowski, "The significant effect of warmer weather on cognition should be considered when designing and conducting clinical trials. This information might assist clinicians in choosing clinical treatment, and help researchers develop effective strategies for coping with the negative effects of weather-related effects on cognition that impact independence, education, employment and activities of daily living."
Source: Science Daily Copyright 2013 by ScienceDaily, LLC (01/11/13)
Measuring the walking speed of multiple sclerosis patients can help doctors assess progression of the disease and the severity of disability, a new study suggests.
In people with multiple sclerosis (MS), the immune system damages the protective myelin sheath around the body's nerves.
"We already know that the timed 25-foot walk test is a meaningful way to measure disability in MS," study author Dr. Myla Goldman, of the University of Virginia in Charlottesville, said in a news release from the American Academy of Neurology. "Our study builds on that research by providing a clearer idea of how walk time can provide information about how a person's disease progression and disability impacts their everyday activities and real-world function."
The study included 254 MS patients who were timed as they walked 25 feet. Those who took longer than 6 seconds to walk that distance were more likely to be unemployed, to have changed jobs because of MS and their walking ability, to use a cane, and to require help with daily activities such as cooking and house cleaning.
For example, 59 percent of those who took less than 6 seconds to walk 25 feet were employed, compared to 29 percent of those who took longer than 6 seconds. Just 43 percent of the faster walkers had changed jobs because of MS, compared to 71 percent of slower walkers.
Patients who took 8 seconds or longer to walk 25 feet were more likely to be unemployed, to use Medicaid or Medicare, be divorced and use a walker. They were more than 70 percent more likely to be unable to perform daily activities such as house cleaning, grocery shopping, laundry and cooking, according to the study published online Oct. 30 in the journal Neurology.
Based on the study findings, "we propose that a timed 25-foot walk performance of 6 seconds or more and 8 seconds or more represent meaningful benchmarks of MS progression," Goldman added in the news release.
Source: US News Health Copyright © 2013 U.S. News & World Report LP (31/10/13)
Research group raises funds for MS study(31/10/13)
A new group based in the Northern Isles, where the highest prevalence of multiple sclerosis in the world is found, is to raise money to fund research into the disease.
The Shetland and Orkney Multiple Sclerosis Research Project recently acquired charity status as a fund raising organisation.
The money raised by the group will help fund a PhD student at Edinburgh University, who will undertake further research into possible causes of MS.
The data to be used was obtained during genetic studies in the Northern Isles, set up to investigate how important inherited factors might be in causing MS.
The money raised in the two communities will be match-funded by the Centre for Population Studies at Edinburgh University and the project will be led by Dr Jim Wilson, a well-known Orcadian geneticist.
Source: HeraldScotland © Copyright 2013 Herald & Times Group (31/10/13)
Researchers in Milan, Italy reported that stem cells derived from mouse skin tissue were able to reduce nervous system damage in mice with a disease similar to multiple sclerosis, offering further evidence for the possibility that stem cells from patients might in the future be used for cell therapy to treat MS. The study, by Cecilia Laterza, Ph.D., Gianvito Martino, MD and colleagues at the San Raffaele Scientific Institute, Milan, and the University of Milan, was published today in Nature Communications.
The study was co-funded by the National Multiple Sclerosis Society, Multiple Sclerosis Italian Foundation (FISM), MIUR Lombardy Region (NetLips Project), ELA Foundation, BMW Italy and NEUROKINE network (EU Framework 7 ITNproject).
Current therapies for MS reduce the immune system attacks that damage the brain and spinal cord, but they are not effective in progressive phases of the disease, when damage to the protective myelin coating on nerve fibers and the nerve fibers themselves may be widespread. Finding ways to repair the nervous system to restore function is a major research priority.
For this study the team used mouse skin stem cells and forced them through "cell reprogramming" to become myelin-making cells. This technique allows differentiated (specialized) cells, such as skin cells, to become embryonic-like stem cells which can become any kind of cell, including neural stem cells, the stem cells of the brain.
As in previous studies of this type, after the cells were infused into the spinal cord, they promoted recovery in mice with the MS-like disease EAE (experimental autoimmune encephalomyelitis). Transplanted cells were able to reduce inflammation and protect the intact myelin from further damage, and were also able to foster the production of new myelin by the brain's own cells. The team further showed that the protective effect was mediated by a soluble factor released by the transplanted cells, called "leukemia inhibitory factor."
"Our discovery opens new therapeutic possibilities for multiple sclerosis patients because it might target the damage to myelin and nerves itself," stated study leader Dr. Gianvito Martino.
"This is an important step for stem cell therapeutics," noted Dr. Timothy Coetzee, Chief Research Officer of the National MS Society. "The hope is that skin or other cells from individuals with MS could one day be used as a source for reparative stem cells, which could then be transplanted back into the patient without the complications of graft rejection," he added.
More work is needed, but this type of research gives hope that this strategy may eventually help restore lost function. Read more about research to repair the nervous system.
"There is still a long way to go before reaching clinical applications but we are getting there," said Dr. Martino. "We hope that our work will contribute to widen the therapeutic opportunities stem cells can offer to patients with multiple sclerosis."
"This is an important result for people with MS: rigorous basic science providing insights into the mechanisms involved in myelin and nerve damage is the only way to foster the discovery of new therapies for progressive forms of the disease," noted Paola Zaratin, Ph.D., Director of Scientific Research at the Italian MS Society/Italian MS Foundation.
Source: The Sacramento Bee Copyright © The Sacramento Bee 2013 (30/10/13)
Objective: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with multiple sclerosis (MS).
Methods: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry.
Results: Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive patients with MS compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus–1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in patients with MS; however, no specific EBV genetic variant was preferentially associated with MS.
Conclusion: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV.
Carmen Yea, MSc, Raymond Tellier, MD, Patrick Chong, PhD, Garrett Westmacott, PhD, Ruth Ann Marrie, MD, PhD, Amit Bar-Or, MD, Brenda Banwell, MD; On behalf of the Canadian Pediatric Demyelinating Disease Network
Source: Neurology © 2013 American Academy of Neurology (30/10/13)
While it's been known for over a century that iron deposits in the brain play a role in the pathology of Multiple Sclerosis (MS), new imaging research from Western University (London, Canada) helps to answer the question of whether these accumulations are a cause or consequence of the disease. The study led by Ravi Menon, PhD, of the Robarts Research Institute found iron deposits in deep gray matter, suggesting the accumulation occurs very early in the disease course. The researchers also found evidence casting further doubt on the controversial liberation therapy for MS. The research is in early publication online in Multiple Sclerosis and Related Disorders.
Menon and PhD candidate Matthew Quinn used 3-Tesla Magnetic Resonance Imaging (MRI) to scan 22 patients with clinically isolated syndrome (CIS). These are patients who've had a single clinical attack, at least half of whom will go on to be diagnosed with MS. The others may have a different disease. Sixteen age and sex matched controls were also studied.
"We wanted to know if the iron deposits happen early in the process, or whether it's something that accumulates with time as the disease progresses," says Menon, who holds a Canada Research Chair in Functional Magnetic Imaging. "We also studied the veins that drain from the brain and looked for a correlation between the diameter of of these veins and iron accumulation. One of the reasons to do this, of course was the hypothesis proposed by Paolo Zamboni that if you had narrow jugular veins, this would give rise to additional iron and in turn cause MS."
The scientists found iron deposits in the CIS group were well above the amounts found in the control group. The MRIs also revealed for the first time, subtle damage to the brain's white matter even at this early stage. The researchers also found no correlation between the iron deposits and diameter of the veins.
"So while the iron in the brain correlates with the disability of the subjects, the iron in the brain does not correlate with the actual diameter of the jugular veins. So the Zamboni hypothesis is incorrect as far as the iron being related to some kind of obstruction." Menon found narrowed veins in the control group as well as the CIS group, and both groups had narrower veins on one side compared to the other.
Menon hopes this imaging research will lead to the earlier diagnosis of MS. He plans to follow the patients every four months for the next two years, to see retrospectively, what characterizes those patients that go on to be diagnosed with MS compared to those who do not.
"We're looking at a couple of different approaches to diagnostics using this imaging research. In suspected MS cases –the very first time they appear in clinic, if they have an abnormally high amount of iron in the frontal cortex of the brain –that's probably a pretty good sign they have MS or some other white matter disease." This research was funded primarily by the Canadian Institutes of Health Research.
MS is the most common neurological disease affecting young adults, with symptoms that include loss of balance, impaired speech, double vision, extreme fatigue and paralysis.
Source: MedicalXpress © Medical Xpress 2011-2013, Phys.org network (29/10/13)
Jason McIntyre's autoimmune system is dead. The rest of him isn't feeling much better. Eleven days ago he underwent an aggressive chemotherapy, not for the sake of killing cancer - but to knock out every skerrick of protection his body has against infection.
Sitting in a freezer were 35 million stem cells that were shaken from Mr McIntyre's bone marrow by a combination of drugs. These were filtered from his blood about three weeks ago. That process, he says, left him with aching bones. It was his birthday.
If he survives long enough - that is, if a piece of dust doesn't get in his eye and spark a fatal infection - the stem cells will this week be returned to his body, as building blocks for a brand new autoimmune system.
Mr McIntyre, 37, is only the sixth patient with multiple sclerosis to undergo this experimental therapy - known as an autologous haematopoietic stem cell transplant - in a small trial being conducted by St Vincent's Hospital in Sydney.
Thousands of stem cell transplants are performed worldwide to treat certain blood cancers in patients who have become resistant to regular therapies - but the numbers of MS sufferers treated with a stem cell transplant are in the hundreds.
It's a strategy reserved for people like Jason McIntyre whose form of MS is very aggressive and resistant to drug therapy.
About three years ago, the Melbourne truck driver arrived home with blurry vision. He told his wife, Kym, that he couldn't read the number plates on cars. Soon after, following a session at the gym, he was ''boiling hot and his vision went blurry again''.
Kym McIntyre says it all happened pretty quickly. He started dragging his left foot. He couldn't unscrew bottle tops and lost his co-ordination.
An eye doctor recognised the problem as multiple sclerosis, but Mr McIntyre was told by a specialist that he'd have to wait for another attack - another lesion on the brain to develop - for the diagnosis to be confirmed.
Meanwhile, the trucking company Mr McIntyre ran with his father, Peter, had to stay in business. Peter was meant to be retiring, but went back on the road. The McIntyres have two small children, and the medical bills aren't going away.
When the diagnosis was confirmed, Mr McIntyre underwent a series of injections to alleviate symptoms and slow the attacks. It didn't work. He was put on a more aggressive drug therapy. That didn't work either, and his body went into further decline. His specialist said he had run out of options.
''Jason's sister Stacey didn't cop that,'' says Ms McIntyre. ''She went online and found a transplant trial was happening in Canberra.'' However, that project collapsed because of lack of funding.
Then came word that the haematopoietic stem cell transplant team at St Vincent's Hospital in Sydney - where patients with blood cancers are routinely treated - were trialling the treatment with MS sufferers who weren't responding to traditional therapies.
Speaking from his hospital bed, Mr McIntyre said the chemotherapy was ''knocking me about a bit. Feeling tired. See how we go.''
His wife was upbeat - or perhaps driven is a better word. ''I'm sick of chasing the kids. I need him back in action.''
The children, Pyper, 6, and Ryder, 3, were at an apartment with Ms McIntyre's mother. They were anxious and rowdy. ''They just want everything to get back to normal.'' Stem cell transplants have a claimed 70 per cent success rate at halting some types of MS. However, researchers here and abroad can't get sufficient funding such that a randomised trial can be undertaken that would bring the treatment into the mainstream.
''There have been many attempts in Europe to mount good clinical studies to demonstrate definitively that the transplants are effective, but [the studies] weren't successful … each time they ran out of money,'' says Professor David Ma, the head of the St Vincent's haematopoietic stem cell transplant team, which is caring for Mr McIntyre.
The St Vincent's small-scale trial is part of an international effort to get enough runs on the board - and secure funding.
Multiple sclerosis, says Professor Ma, is a good fit for stem cell transplant therapy because it's an autoimmune disease.
The brain and spinal cord become inflamed with lesions - and these are then attacked and damaged by the autoimmune system. If the immune system can be effectively killed off, and replaced with a new system, then the brain has an opportunity to recover from the inflammation that caused the problem in the first place.
''It's a radical strategy, for sure,'' says Professor Ma. ''We're trying to get it past the experimental stage.''
Lisa Melton, research development manager with MS Research Australia, said about 40 patients in Australia were known to have undergone the therapy, with mixed results. Most of the treatments were carried out at the discretion of treating doctors on compassionate grounds at different centres around the country.
''It's a dangerous procedure, highly aggressive, and carries considerable risks,'' says Dr Melton.
MS Research Australia is funding a database to record outcomes in Australian cases.
Source: The Age National Copyright © 2013 Fairfax Media (28/10/13)
OBJECTIVE: The purpose of this study was to assess the safety and efficacy of mitoxantrone (MX) in pediatric patients with aggressive multiple sclerosis (MS).
METHODS: A retrospective analysis on pediatric MS patients treated with MX was performed with regards to demographic/clinical parameters and magnetic resonance imaging (MRI) findings.
RESULTS: 19 definite pediatric MS cases with mean ± SD age of 15.4 ± 2.8 years underwent 20 mg MX for control of their severe/frequent relapses, high EDSS score or new and active brain MRI lesions. After a median [IQR] follow-up period of 30[12-60] months, 14 cases (73%) were relapse free; the EDSS score decreased by at least 0.5 in 16 cases (84.2%); and gadolinium-enhancing lesion volume fell by 84.2% in 16 cases. Adverse events included nausea and vomiting, fatigue, alopecia, palpitation, cardiomyopathy and mild leukopenia. All adverse events were mild and transient.
CONCLUSION: Our results suggest MX is a good candidate for treatment of children with worsening RRMS and SPMS. Recommendations regarding patient selection, treatment administration, and close follow-up should be considered. Continuing research is needed to establish its efficacy and safety profile in a multinational collaboration with careful follow-up of adverse events.
Etemadifar M, Afzali P, Abtahi SH, Ramagopalan SV, Nourian SM, Murray RT, Fereidan-Esfahani M.
Department of Neurology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran; Isfahan Research Committee of Multiple Sclerosis (IRCOMS), Isfahan University of Medical Sciences, Isfahan, Iran.
Sources: Eur J Paediatr Neurol. 2013 Oct 7. pii: S1090-3798(13)00131-1. doi: 10.1016/j.ejpn.2013.09.001. [Epub ahead of print] Copyright © 2013 European Paediatric Neurology Society & Pubmed PMID: 24139067 (28/10/13)
Light as medicine?(23/10/13)
Multiple sclerosis (MS) causes progressive paralysis by destroying nerve cells and the spinal cord. It interrupts vision, balance and even thinking.
On a suggestion from a colleague, Jeri-Anne Lyons decided to test how the disease responded to a radical therapy – exposure to a certain wavelength of light called near-infrared (NIR).
"Never in a million years did I think it would help," says Lyons, an associate professor of biomedical sciences at the University of Wisconsin-Milwaukee (UWM), who studies the role of the immune response in MS.
But it did. In rodent models, early MS-like symptoms were treated with exposure to NIR light for a week, alternating with a week of no light. The clinical condition of the mice improved.
Professor Janis Eells, who shared the idea with Lyons, had the same initial reaction after she used NIR therapy on rats to treat blindness caused by poisoning, a condition thought to be permanent. Repeating experiments again and again, she found that certain doses of NIR light allowed lab animals to regain their sight.
Scientists have known for years that certain wavelengths of light in certain doses can heal, but they are only now uncovering exactly how it works, thanks in large part to three UWM faculty researchers, including Chukuka S. Enwemeka, dean of UWM's College of Health Sciences who is internationally known for his work in phototherapy.
Enwemeka researches the effects of both NIR and blue light in the visible range on healing wounds. Among his discoveries is that some wavelengths of blue light can clear stubborn infections – even MRSA, the antibiotic-resistant "superbug" form of Staphylococcus aureus.
Together, the UWM cluster has found that NIR and blue light repair tissue in dramatically different ways, but both act on the same enzyme in the cell's energy supply center: the mitochondria.
The studies have revealed key information about managing the effects of aging and disease.
So how is light accomplishing such wonders?
In applying NIR light therapy to MS, Lyons has identified the right timing and dose. But she's also dug deeper, analyzing the effect the light had on the activities of the animal's genes. It turns out, molecules that would make the disease worse were weakened after exposure to the light, and the ones responsible for improvement were strengthened.
Eells says NIR light acts on the mitochondria and a particular enzyme, cytochrome C oxidase, to stimulate cell repair.
Light can do all that?
"We're not talking about white light [all wavelengths in the visible spectrum combined] as treatment, but only certain wavelengths, at a certain intensity, for a certain amount of time," says Lyons. "Like ingested medication, it's all about the dose."
Determining the best wavelength of light for phototherapy is a difficult task. Studies show that 670 nanometer (nm) and 830 nm light are beneficial, but 730 nm is not. The other difficult task is determining the appropriate dose and dose regimen for delivering the light.
Even more exciting is phototherapy's potential to improve a host of other degenerative diseases. Damaged mitochondria lead to a rise in destructive "free radicals," which play a key role in aging and cancer.
"It's why we try to put antioxidants into our diets," says Lyons, "to fight that process."
One source of free radicals comes from the inflammation caused by the body's immune response. The researchers have found that after an injury or illness triggers the immune response, NIR light resets the mitochondria so they function normally again.
"NIR reduces inflammation," says Eells. "If you can tone down the inflammation in an eye disease like retinitis pigmentosa, you slow the progression of the disease."
A similar observation with inflammation occurred in a study on recalcitrant bedsores, she adds. Wounds treated with phototherapy healed two and a half times more quickly than untreated wounds.
"Chronic non-healing wounds are 'stuck' in the inflammatory phase of wound healing" The light removes that obstacle," says Eells.
She has been working with Tim Kern at Case Western Reserve in treating an animal model of diabetic retinopathy with NIR light, which has been shown to slow progression and reduce the severity of the condition. Kern hopes to initiate a clinical trial in the near future.
NIR light heals by ensuring that cytochrome oxidase binds with oxygen to turn on protectors and stimulate cell metabolism. Blue light, on the other hand, causes a toxic environment when the immune response has been triggered. That poisonous effect hastens healing of topical wounds by killing bacteria that cause infection.
The question is, "What gives light in the longer wavelength its antibiotic effect?"
Enwemeka's studies suggest that blue light also acts on the mitochondrial enzyme site, but allows cytochrome oxidase to bind with nitric oxide, a free radical that is elevated in the immune response. It's a pairing that poisons the invader.
This theory is still unproven, but the therapy has achieved undeniable results in the lab with antibiotic-resistant MRSA. Enwemeka demonstrated that one dose of irradiation killed as much as 92 percent of two pervasive strains of MRSA.
He is working to improve that success rate by getting the light to penetrate deeper in order to finish off the few colonies that survive irradiation.
Enwemeka is leading a research effort in Brazil and at UWM that he hopes will ultimately lead to clinical use of NIR and blue light in the U.S. for the treatment of wounds. In the six years since he was asked to test the effects of blue light on MRSA, he says, research on the topic has picked up. But currently, the U.S. Food and Drug Administration (FDA) has not sanctioned the use of blue light in treating wounds, or NIR light for conditions other than wounds and pain.
With so much success, why isn't phototherapy being used more widely?
"It's considered alternative therapy in Western medicine. It seems too simple for people to accept," says Lyons.
What the FDA is waiting for, says Enwemeka, is confirmation from a large-scale clinical study before approving phototherapy for a wider variety of ailments. It's something Enwemeka and Harry Whelan, a UWM alumnus and physician-researcher at the Medical College of Wisconsin, are determined to accomplish.
"To see people who have not had relief see their wounds heal and not return," says Enwemeka of the Brazilian patients who have benefited from therapy, "is very touching."
Source: Science Codex (23/10/13)
The FDA is continuing to investigate a possible link between the multiple sclerosis drug Gilenya (fingolimod) and a case of a rare brain infection in a European patient.
The patient took the drug for nearly 8 months before being diagnosed with the brain infection. The FDA issued an alert at the end of August to inform the public of its investigation.
The brain infection, sometimes fatal, is called PML (progressive multifocal leukoencephalopathy). The European case is the first reported in a patient who has not previously taken the drug Tysabri (natalizumab). Tysabri is already known to be linked with a higher risk for PML.
The maker of Gilenya, Novartis, issued a statement saying it had reviewed all available evidence and that the case of PML in Europe is unlikely to be linked to the drug.
Gilenya, approved by the FDA in 2010 for relapsing MS, is taken by mouth. It is one of three new oral drugs approved in the last 3 years. The other two are Tecfidera (dimethyl fumarate) and Aubagio (teriflunomide).
In MS, the immune system attacks the central nervous system, including the brain, spinal cord, and optic nerves.
According to the FDA, patients should not quit taking Gilenya without talking to their doctor.
The FDA will issue its findings once the investigation is complete.
Source: WedMD ©2005-2013 WebMD, LLC. (21/10/13)
GW Pharmaceuticals plc, today announced the successful closing of the European Mutual Recognition Procedure (MRP) in France for Sativex(R) oromucosal spray in the treatment of spasticity due to Multiple Sclerosis (MS) and a resulting recommendation for approval by the French authorities.
The next step in the regulatory process is to work with the French National Agency of Medicine and Health Products Safety (ANSM) to finalize any country-specific requirements. Following completion of this next step, it is then expected that France will issue a national marketing authorisation. Launch timing in France is dependent on completion of subsequent national pricing and reimbursement procedures. Sativex will be commercialized in France by GW's European partner, Almirall S.A.
"The successful completion of this regulatory process for Sativex in France maintains our positive regulatory track record for Sativex, which is already approved in 22 countries, and provides further endorsement of the important role Sativex can play in meeting a substantial unmet need of people with Multiple Sclerosis," stated Justin Gover, Chief Executive Officer of GW Pharmaceuticals. "We look forward to working with our partners, Almirall, towards the launch of Sativex in this important European country." Sativex is approved as a treatment for MS spasticity in 22 countries, including 17 countries in Europe. The medicine is currently available on prescription in the UK, Spain, Germany, Canada, Denmark, Norway, Israel, Austria, Poland, Sweden, Italy and Finland with launches currently in preparation for a further 8 European countries, as well as Australia, New Zealand and Kuwait.
In the United States, GW announced in August 2013 that it had opened a Phase 3 Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to conduct a pivotal efficacy and safety clinical program to evaluate Sativex(R) for the treatment of MS spasticity. GW expects the U.S. Phase 3 trial to commence in 2014.
Sativex is also currently in Phase 3 clinical trials as a treatment for cancer pain. This represents the lead target indication for the product in the United States.
Source: GW Pharmaceuticals plc (21/10/13)
Latest results from the clinical trial program with BG-12 (dimethyl fumarate; Tecfidera, Biogen Idec) suggest sustained clinical efficacy and safety in patients with multiple sclerosis (MS) taking the drug for up to 4 years.
In addition, a separate post hoc analysis of the phase 3 pivotal Determination of the Efficacy and Safety of Oral Fumarate in Relapsing–Remitting MS (DEFINE) and Comparator and an Oral Fumarate in Relapsing–Remitting Multiple Sclerosis (CONFIRM) clinical trials shows that BG-12 reduced relapses and disease activity in treatment-naive patients.
The latest long-term results come from the ENDORSE study, an extension phase of the DEFINE and CONFIRM trials.
Commenting on these results for Medscape Medical News, Bernd Kieseier, MD, Heinrich Heine University, Düsseldorf, Germany, who did a talk rounding up meeting highlights including these new results, said, "These are reassuringly meaningful clinical results showing that the effects of BG-12 over 2 years are maintained in the third and fourth year, with no additional safety concerns."
Ralf Gold, MD, St. Josef-Hospital/Ruhr-University in Bochum, Germany, a leading investigator in the extension study, said, "When making MS treatment decisions, we weigh efficacy and safety considerations, so it is encouraging to see that the positive profile of BG-12 observed in the DEFINE and CONFIRM studies has been maintained in the ENDORSE clinical trial to date."
These data were presented at the recent 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Newest Oral Therapy
BG-12 is one of the new oral therapies for multiple sclerosis. It was approved by the US Food and Drug Administration in the United States and is going through the reimbursement process in Australia and Canada.
In Europe, regulatory authorities are still reviewing the drug, with "data exclusivity" discussions ongoing. Biogen told Medscape Medical News that it has strong patent protection for the product, but the company is in discussions with the European authorities on regulatory data protection "to ensure maximum coverage is in place."
Of the 2651 patients who participated in DEFINE and CONFIRM, 1736 were enrolled in ENDORSE. Patients who received BG-12 in the DEFINE or CONFIRM studies continued receiving the drug at the same dosage — twice daily (BID) or 3 times daily (TID) — in ENDORSE. Patients who received placebo in DEFINE or glatiramer acetate (GA) in CONFIRM were randomly assigned to BG-12 BID or TID.
Interim efficacy results at 2 years into ENDORSE suggest efficacy and safety of BG-12 similar to those shown in the DEFINE and CONFIRM studies.
Professor Kieseier commented to Medscape Medical News: "The obvious question at the end of a 2-year clinical trial is: 'Will these results be maintained over time?' We can see from these latest results that the benefit has been maintained, and in the patients switched from placebo or glatiramer acetate the annual relapse rate has come down to a similar level as those who were taking BG-12 long-term."
He added: "Of course, it would be nice to have a comparison with placebo long term but this can't be done, so the closest we can get is to follow patients to see if a low level of disease activity continues and that seems to be the case. We are seeing a similar relapse rate in the third and fourth years as we did in the first and second year of BG-12 treatment. That is encouraging."
Professor Kieseier noted that annual relapse rates of 0.1 to 0.2, as seen in ENDORSE, are typical of what is achieved with other long-term effective drug therapies. "We don't have a drug that gets this down to zero," he said.
In terms of safety, no new adverse effects were reported in patients continuing to receive BG-12 in ENDORSE. The most common adverse events in patients who were switched to BG-12 from placebo or GA were flushing and gastrointestinal events, the incidences of which were generally similar to those observed in DEFINE and CONFIRM, Biogen reports. The most common adverse event in patients continuing to receive long-term BG-12 is nasopharyngitis (common cold).
Similar to what was seen in CONFIRM and DEFINE, mean lymphocyte counts in patients who switched to BG-12 in ENDORSE decreased over the first year of treatment and then plateaued. The incidence of lymphocyte counts 0.5 × 109/L was 6% to 8% in the continued BG-12 groups and 5% to 9% in the new-to-BG-12 groups.
For patients who continued treatment with BG-12, mean lymphocyte counts were generally stable and mean counts remained within normal limits at all time points, the researchers note. They add that there was no overall increased risk for serious infections or malignancies in patients continuing to receive, or new to, BG-12 treatment. And there was no overall increased risk for renal dysfunction or hepatic adverse events in any treatment group.
Asked about the lymphocyte count reduction, Professor Kieseier said, "It is something that needs to be considered, but I don't think it is a major concern. The other drugs also show this effect. But it seems to happen relatively infrequently with BG-12."
He added that BG-12 did not seem to have severe toxicities. "Patients will appreciate that. The driving interest in this drug at the moment is its good efficacy paired with good tolerability, and these results show that this profile continues to be there in the long-term."
MRI results from ENDORSE showed continued that treatment with BG-12 resulted in a low frequency of new/enlarging T2 hyperintense lesions, new nonenhancing T1 hypointense lesions, and gadolinium-positive lesions over 4 years. Patients initially randomly assigned to placebo or GA who then received BG-12 in ENDORSE demonstrated MRI outcomes similar to those observed with BG-12 treatment in the parent studies.
In a separate post hoc analysis from the phase 3 DEFINE and CONFIRM studies of 678 new treatment-naive patients with MS, BG-12 was associated with a 50% reduction in relapse rate compared with placebo. Patients taking BG-12 also had a significantly reduced risk for disability progression and a significant positive effect on MRI outcomes in this patient population.
Several researchers involved in these studies are employees of Biogen Idec. Dr. Gold receives honoraria and/or research support from Bayer, Biogen Idec, Merck Serono, Novartis, and Teva. Professor Kieseier has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Health Care, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, sanofi-aventis, and TEVA.
29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Poster #538, #990, #996, and #1004.
Source: Medscape Multispecialty Copyright © 1994-2013 by WebMD LLC (18/10/13)
Glatiramer acetate (GA) is a mixture of synthetic peptides used in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to investigate the effects of GA therapy on the gene expression of monocytes.
Methods: Monocytes were isolated from the peripheral blood of eight RRMS patients.
The blood was obtained longitudinally before the start of GA therapy as well as after one day, one week, one month and two months. Gene expression was measured at the mRNA level by microarrays.
Results: More than 400 genes were identified as up-regulated or down-regulated in the course of therapy, and we analyzed their biological functions and regulatory interactions.
Many of those genes are known to regulate lymphocyte activation and proliferation, but only a subset of genes was repeatedly differentially expressed at different time points during treatment.
Conclusions: Overall, the observed gene regulatory effects of GA on monocytes were modest and not stable over time. However, our study revealed several genes that are worthy of investigation in future studies on the molecular mechanisms of GA therapy.
Author: Madhan Thamilarasan, Michael Hecker, Robert Hermann Goertsches, Brigitte Katrin Paap, Ina SchrÃ¶der, Dirk Koczan, Hans-Jorgen Thiesen,Uwe Klaus Zettl
Credits/Source: Journal of Neuroinflammation 2013, 10:126
Source: 7thSpace Interactive © 2013 7thSpace Interactive (18/10/13)
A research team from Weill Cornell Medical College and The Rockefeller University has identified a bacterium it believes may trigger multiple sclerosis (MS), a chronic, debilitating disorder that damages myelin forming cells in the brain and spinal cord.
Their study, published in PLoS ONE, is the first to identify the bacterium, Clostridium (C.) perfringens type B, in humans.
The scientists say their study is small and must be expanded before a definitive connection between the pathogen and MS can be made, but they also say their findings are so intriguing that they have already begun to work on new treatments for the disease.
"This bacterium produces a toxin that we normally think humans never encounter. That we identified this bacterium in a human is important enough, but the fact that it is present in MS patients is truly significant because the toxin targets the exact tissues damaged during the acute MS disease process," say the study's first author, K. Rashid Rumah, an MD/PhD student at Weill Cornell Medical College, and the study's senior investigator, Dr. Timothy Vartanian, professor of neurology and neuroscience at Weill Cornell Medical College and director of the Judith Jaffe Multiple Sclerosis Center at New York-Presbyterian Hospital/Weill Cornell Medical Center.
"While it is clear that new MS disease activity requires an environmental trigger, the identity of this trigger has eluded the MS scientific community for decades," Dr. Vartanian says. "Work is underway to test our hypothesis that the environmental trigger for MS lays within the microbiome, the ecosystem of bacteria that populates the gastrointestinal tract and other body habitats of MS patients."
Connection to MS in grazing animals
The study describes discovery of C. perfringens type B in a 21-year-old woman who was experiencing a flare-up of her MS.
The woman was part of the Harboring the Initial Trigger for MS (HITMS) observational trial launched by Dr. Vartanian and K. Rashid Rumah, who works both with Dr. Vartanian and with co-author Dr. Vincent Fischetti at The Rockefeller University.
C. perfringens, found in soil, is one of the most common bacteria in the world. It is divided into five types. C. perfringens type A is commonly found in the human gastrointestinal tract and is believed to be largely harmless.
C. perfringens types B and D carry a gene (epsilon toxin) that emits a protoxin -- a non-active precursor form of the toxin -- which is turned into the potent "epsilon" toxin within the intestines of grazing animals. The epsilon toxin travels through the blood to the brain, where it damages brain blood vessels and myelin, the insulation protecting neurons, resulting in MS-like symptoms in the animals.
While the D subtype has only been found in two people, based on prior studies by other investigators, the B subtype had never been found in humans.
Nevertheless, Rumah and the research team set out to see if subtypes B or D exist in humans and if they are associated with MS. They tested banked blood and spinal fluid from both MS patients and healthy controls for antibody reactivity to the epsilon toxin. Investigators found that levels of epsilon toxin antibodies in MS patients were 10 times higher than in the healthy controls -- the blood of only one out of 100 control participants showed an immune reaction to the toxin.
The team also examined stool samples from both MS patients and healthy controls enrolled in the HITMS clinical study, and found that 52 percent of healthy controls carried the A subtype compared to 23 percent of MS patients. "This is important because it is believed that the type A bacterium competes with the other subtypes for resources, so that makes it potentially protective against being colonized by epsilon toxin secreting subtypes and developing MS," say Rumah and Vartanian.
The search by investigators for evidence of C. perfringens type B paid off in the case of a young MS patient. Co-author Dr. Jennifer Linden, a microbiologist at Weill Cornell Medical College, isolated the actual bacterium from the patient's stool.
A choice of approaches for treatment
The authors suspect that once a human is infected with C. perfringens type B or D, the pathogen usually lives in the gut as an endospore, a seed-like structure that allows some bacteria to remain dormant for long periods. "The human gastrointestinal tract is host to approximately 1,000 different bacterial species, but is not a hospitable environment for C. perfringens type B or D, so it does not grow well there. It hibernates in a protective spore. When it does grow, we anticipate it generates a small quantity of epsilon toxin, which travels through the blood into the brain," Dr. Vartanian says. "We believe the bacterium's growth is episodic, meaning the environmental trigger is always present, and it rears its ugly head from time to time."
He says researchers do not know how humans are infected with C. perfringens type B or D, but they are studying potential routes of exposure. The scientists are also in the first stages of investigating potential treatments against the pathogen.
"There are a variety of approaches we can take. A vaccine for humans is possible -- there is already a vaccine available for farm animals, but it requires repeat immunizations," say Vartanian and Rumah. "We are also investigating the possibility of developing small-molecule drugs that prevent the toxin from binding to its receptor.
"But one of my favorite approaches is development of a probiotic cocktail that delivers bacteria that compete with, and destroy, C. perfringens types B and D," Vartanian says. "It would be such a beautiful and natural way to treat the gastrointestinal system and solve the problem. We are also starting to work on this approach."
Source: Copyright © Health News Digest, 1999 (16/10/13)
FOR Sam Sheppard, the first signs that a relapse of her multiple sclerosis (MS) is on its way, are tingling, numbness and pain in her hands and feet.
When that happens, the mum-of-two from Surrey, gets straight on the phone to her specialist MS nurse. “A big relapse is devastating,” says Sam, 39, who works as an administrator.
“When a relapse strikes it’s not just me that is affected, I can’t get out of bed, I can’t get the kids to school, I need time off work and my husband has to become mum and dad for the family.
“I’ve got a great nurse who always says ‘if in doubt give me a shout’. If I don’t tell him about these minor symptoms, we can’t make the right decisions about my treatment options.”
Unfortunately not all MS patients are quite so vigilant. A new UK study has revealed that nearly half (46 per cent) of patients suffered a relapse but did not tell anyone.
Researchers of the Novartis-funded MS Pathways study also found that specialist MS doctors and nurses were accepting relapses as inevitable and without considering alternative treatments.
So experts are now urging patients to report even minor relapses to their doctor because of the catastrophic effect it could have on their health, finances and family life.
Study leader Dr Martin Duddy, consultant neurologist at Royal Victoria Infirmary in Newcastle, says: “Even minor relapses have an impact on a patient’s physical and psychological well being, as well as their financial well being.
“We need to have a clear picture of whether or not patients are having relapses, as they have an important role in assessing whether they need treatment and whether that treatment is working.”
MS is the most common neurological condition affecting young adults in the UK. It is estimated that 100,000 people in the UK have MS. Relapsing remitting MS (RRMS) is the most common form, affecting 80 per cent of people.
Relapses are unexpected and can happen at any time. The impact can last for weeks or months. Symptoms may range from loss of vision to spasm and mobility problems.
It can have a huge impact on family life, work and social activities.
A third of patients in the study reported a reduction in family income while nearly half had to temporarily reduce their hours and 10 per cent had to give up work entirely.
The main reasons cited for under-reporting were that patients considered their symptoms too mild or did not feel there was anything their doctor or MS nurse could do about it.
But Amy Bowen, Director of the MS Trust says: “It is crucial that we improve reporting of relapses and ensure that people with MS receive the right information about recognising a relapse and the treatment that is available to help them manage its impact.
“No one should be coping with the burden and disruption of a relapse without the support of their MS team, particularly their MS specialist nurse.”
Source: Copyright ©2013 Northern and Shell Media Publications."Daily Express" is a registered trademark. All rights reserved. (16/10/13)
Written by Jeri Burtchell | Published on 16 October 2013
The influenza vaccine is recommended for MS patients, but only if they receive it in shot form and are not taking steroids.
Flu season is upon us, and people with multiple sclerosis (MS) are once again debating whether or not to get vaccinated. According to the National Multiple Sclerosis Society (NMSS), they absolutely should.
“The injectable flu vaccine, which is an ‘inactivated’ vaccine, is recommended for everyone over six months of age,” the NMSS states, “It has been studied extensively in people with MS and is considered quite safe.
"The injectable flu vaccine may be taken by people who are taking an interferon medication, glatiramer acetate, mitoxantrone, natalizumab, or fingolimod. However, it is not yet know whether the vaccine is as effective for those taking natalizumab or fingolimod.”
There is no chance of catching the flu from the injectable vaccine because it uses a dead virus. This is unlike the FluMist® nasal spray, which uses a live, replicating virus. The NMSS does not recommend the nasal spray for MS patients.
“When thinking about having the flu vaccine, you should talk to your neurologist to see if the MS medicine that you are on may make your body less responsive to the vaccine,” explains Daniel Kantor, M.D., the former president of the Florida Society of Neurology and the Medical Director of Neurologique, in an interview with Healthline.
“For the self injectables (the beta interferons and Copaxone), there is no bad interaction between the flu vaccine and the medications," he says. "For some of the newer medications, the flu vaccine may not be as effective as it would be otherwise. This is why it is a good idea to have a plan with your neurologist and primary care doctor about what you will do in the flu season.”
Even though the flu shot cannot cause the flu, some people with MS may feel lousy for a few days after they receive it. “If your body temperature gets increased after the vaccine, you may have an uncovering of older MS symptoms,” explains Kantor.
MS patients are often more susceptible to high temperatures because of a process called Uhthoff's Syndrome.
A Few Caveats
Although a flu shot is recommended, there are times when getting one might not be a good idea. “If a person is in the middle of another infection or in the middle of an MS relapse,” says Kantor, “I would probably [postpone] getting a flu vaccine. Also, if a person is allergic to any of the components of the flu vaccine then they shouldn't be vaccinated.”
While the shot is safe for those taking any of the MS disease modifying therapies (DMTs), getting vaccinated while taking steroids is something you should discuss with your doctor.
Vaccines work by introducing small amounts of a substance (in this case, the dead influenza virus) into a person’s system. The immune system then recognizes it as an invader and creates antibodies to attack it. These antibodies are then ready to prevent the infection from taking hold if you are exposed to someone who's sick.
Steroids are often given to MS patients who are relapsing in order to calm the immune system down. But because steroids work by halting the immune response, getting vaccinated during steroid use may not work. The immune system has to respond to the vaccine, and if the immune systems is dormant, antibodies won't form.
However, not being vaccinated and developing the flu while on steroids is a potential risk that also needs to be weighed. “Steroids can suppress your immune system and so put you at greater danger of getting the flu from people around you,” warns Kantor, “thus making vaccination even more important. Steroids can also prevent your body from fighting off the flu virus and so you may be sicker from the virus.”
“This is a perfect example of why medical care is best when it is done in a clinical setting within the doctor-patient relationship,” Kantor adds. “Your doctors can help you weigh the risks vs. benefits of being vaccinated while on steroids, which will also depend on the dose of the steroids and how long you are on steroids for.”
Debunking the Myths
The decision whether or not to vaccinate has been the subject of much debate in the MS community. “Some people are scared of vaccines in general because of a mixture of real risks and conspiracy theories,” Kantor says. “The flu vaccine is probably a good idea for most MS patients, as catching the flu can be disruptive to your life, and the flu vaccine does a fairly good job of helping you avoid the flu.”
Source: Copyright © 2005 - 2013 Healthline Networks, Inc. All rights reserved. (16/10/13)
MONMOUTH JUNCTION, N.J., Oct. 15, 2013 /PRNewswire/ -- Provid Pharmaceuticals Inc. announces a publication in the Journal of Immunology on its promising MS drug candidate, PV-267. The paper, "Small Molecule Inhibitor of Antigen Binding and Presentation by HLA-DR2b as a Therapeutic Strategy for the Treatment of Multiple Sclerosis" is a joint effort of the groups of Prof. Thomas Forsthuber at the University of Texas, San Antonio, Dr. Neil Hayward of Daiamed LLC, and the Provid team, led by Drs. Gary L. Olson and Christopher Self. The paper was published online on October 11, 2013.
The paper presents Provid's novel strategy to inhibit a key pathway in multiple sclerosis that is tied to the genetic profile of patients. PV-267 specifically blocks MHC Class II DR2b (DRB1*15:01), the most important gene target in MS, carried by a majority of patients (ca. 700,000 worldwide). PV-267 blocks the ability of DR2b to bind and present antigenic myelin fragments to autoreactive T cells, disrupting the disease process.
Dr. Forsthuber remarked, "We found PV-267 to be a very effective DR2b blocker but it does not otherwise seem to affect the immune system, indicating a potentially superior safety profile relative to other disease-modifying drugs available to treat MS. The paper describes the design and evaluation of PV-267 in immunological assays in humanized mouse and human cells, and its efficacy in experimental autoimmune encephalomyelitis (EAE), an MS model in DR2b transgenic mice."
Dr. Olson, Provid CEO, commented on the development of PV-267, "The need for effective and safe drugs for multiple sclerosis led us to pursue research leading to PV-267. We are very pleased with the convincing results of efficacy and immunological safety that have emerged from our collaboration with Dr. Forsthuber. Our next step is to complete preclinical development studies needed prior to initiation of clinical trials."
The research described was funded through Provid's partnership with Fast Forward, LLC, the venture arm of the National Multiple Sclerosis Society, and by a grant from the National Institute of Neurological Diseases and Stroke.
Provid Pharmaceuticals Inc. is a drug discovery company that has expertise in structure-aided design, medicinal chemistry, and peptide mimetics technology. The company has applied this capability to programs in autoimmune disease, leading to PV-267 for MS.
Source: copyright © 2013 digitaljournal.com (15/10/13)
Over the course of the disease, multiple sclerosis is very often combined with a deteriorating memory and attention deficits. Researchers at the University Department of Radiology and Nuclear Medicine at the MedUni Vienna have now demonstrated by means of a meta-analysis of functional image data that increased activations in the involuntary attention system in the brain are responsible for these disorders in MS patients.
MS patients generally often have problems with fading out what is unimportant. Says head of the study Veronika Schöpf: "They are practically in continuous alarm mode." The attention system is too highly activated and also notices – for example when watching the television or when talking to someone – completely unimportant extraneous noises.
Because of this, concentrating on what is important is completely impossible or only possible to a limited extent. In addition, MS patients find it difficult to look for one specific thing and also find it. This high activation thus also leads to a poor memory and at the same time adversely affects the ability to take in new things.
In a meta-analysis in the top journal "Neuroscience & Biobehavioral Reviews" (Impact Factor 9.44) it has now been possible to prove that functional changes in the brain are responsible for these disorders and that these can also be depicted by means of functional imaging.
"In most people the centre for these activities lies in the right half of the brain, in many MS patients however it lies in the left side of the brain, as it does in many epilepsy patients," says the PhD student and primary author Kathrin Kollndorfer. This knowledge could now feed into the development of personalised treatments for people with multiple sclerosis in order to counteract these cognitive disorders in good time.
With this, the working group at the MedUni Vienna has also achieved a better generalisability of the research results so far with regard to working memory and attention in patients with multiple sclerosis. "Most studies that have so far dealt with this question by means of functional imaging have mostly examined only very small and heterogeneous samples, which clearly differ with regard to age, gender or duration of illness. We have included in our evaluation everything in studies so far," explains Veronica Schöpf.
Multiple sclerosis is an incurable, chronic inflammatory disease of the central nervous system, which develops slowly at first and in later stages leads to greater and greater physical and mental handicaps. According to figures of the Austrian Multiple Sclerosis Society (ÖMSG) about 12,500 people suffer from this disease.
Source: Health Canal (14/10/13)
Financial support given for development of NRP2945 as potential therapy for MS progression(14/10/13)
CuroNZ, an Auckland biotechnology start-up company developing treatments for progressive multiple sclerosis, has been awarded funding of US$ 540,000 from the National Multiple Sclerosis Society through Fast Forward to support preclinical studies needed to develop CuroNZ’s NRP2945 candidate as a potential therapy to protect the nervous system from MS damage.
Current therapies available for treating multiple sclerosis do not adequately treat progressive stages of the disease or directly protect the nervous system from that damage that leads to progression.
The funding will enable CuroNZ to undertake pre-clinical proof of concept, pharmacokinetic and toxicity studies to bring the drug candidate lead NRP2945 closer to an investigational new drug (IND) application. As part of the project, CuroNZ will collaborate with leading research organisations including the University of Auckland and Monash University in Melbourne. With its unique mechanism of action and a pristine safety profile to date, NRP2945 has the potential to act as a neuroprotective agent which might eventually be developed into a product that can help patients with progressive MS, worldwide.
Finding ways to stop MS progression is a strategic priority of the National MS Society’s research program. A key aspect of the Society’s comprehensive approach to driving research progress is the support of promising research discoveries – such as NRP2945 - toward commercial drug development.
About CuroNZ: CuroNZ was founded in 2009 by Dr. Frank Sieg who discovered the drug candidate portfolio called Neural Regeneration Peptides (NRPs) in Germany. He subsequently brought them to New Zealand with the hope of being able to eventually develop products that could benefit patients suffering from the debilitating effects of progressive MS.
Source: Scoop Health News © Scoop Media 2013 (14/10/13)
Latest data from the CARE-MS II extension study show that alemtuzumab (Lemtrada, Genzyme/Sanofi) has a durable effect on disability in multiple sclerosis (MS), with the mean Expanded Disability Status Scale (EDSS) score at 3 years still below that at baseline.
These new data were presented in a poster at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) last week.
Summing up the highlights of the meeting, Bernd Kieseier, MD, Heinrich Heine University, Düsseldorf, Germany, commented on these latest alemtuzumab results: "Of those patients stable at 2 years, almost 50% are stable in the third year without any further treatment and 20% have better disability scores. And of those who improved in the core study 10% improve more in the third year and 42% remain stable."
Dr. Kieseier added: "These data clearly support the view that we have a potent drug here. It has a dramatic effect on EDSS, with some patients actually improving, and this is maintained in third year even without further treatment."
Commenting for Medscape Medical News, Jeffrey Cohen, MD, Cleveland Clinic, Ohio, who was not involved in this analysis, said, "These results tell me that the short-term benefit seen in the trial is maintained after the trial has ended. The drug continues to be beneficial for years after dosing. We have already seen this to be the case in phase 2 trials, where there has been up to 5 years' benefit. So this is no big surprise."
Noting that the mean EDSS score did increase slightly between year 2 and year 3, Dr. Cohen said the change was very small and "the score looks quite stable to me."
The CARE-MS II (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II) trial http://www.medscape.com/viewarticle/773790 randomly assigned patients with active relapsing/remitting MS to treatment with alemtuzumab or interferon β. Alemtuzumab was given as a 12 g/d intravenous infusion on 5 consecutive days at baseline and 3 consecutive days 1 year later.
More than 90% (393 of 423) of patients who had received alemtuzumab, 12 mg, in CARE-MS II and completed the core study entered the extension. Of these, 20% received a further dose during the third year. Fewer than 3% of patients received another disease-modifying therapy in year 3.
In these patients, mean EDSS score increased slightly from year 2 to year 3 but still remained below the baseline score.
At year 3, 70% of alemtuzumab-treated patients had stable or improved EDSS scores from baseline. Results were similar to those seen at year 2.
In addition, 66% of patients had stable or improved EDSS scores from the start of the extension study (end of year 2).
Among patients whose EDSS scores remained stable from baseline to year 2, 67% continued to remain stable or improved from year 2 to year 3. And among patients whose EDSS score improved from baseline to year 2, 53% remained stably improved or improved further from year 2 to year 3.
At year 3, more than one third of patients who had received alemtuzumab in the core study attained improvement in pre-existing disability that was sustained for 6 months, and more than a quarter achieved improvement in pre-existing disability that was sustained for 12 months.
The CARE-MS trials were funded by Genzyme/sanofi aventis. Dr. Kieseier has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Health Care, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, sanofi aventis, and TEVA Pharmaceuticals. Dr. Cohen reports personal compensation for serving as a consultant or speaker from Biogen Idec, Elan, Novartis, Teva, and Vaccinex and research support paid to his institution from Biogen Idec, Consortium of MS Centers, US Department of Defense, Genzyme, National Institutes of Health, National MS Society, Novartis, Receptos, Synthon, and Teva.
29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Poster presentation #P592. Presented October 3, 2013.
Source: Medscape Copyright © 1994-2013 by WebMD LLC (11/10/13)
Genmab A/S announced top-line results from a Phase II study of the subcutaneous formulation of ofatumumab in relapsing-remitting multiple sclerosis (RRMS).
A total of 232 subjects with RRMS were randomized in the study. There was a clear separation from placebo on the cumulative number of new gadolinium enhancing lesions (active brain lesions) over a period of 12 weeks in subjects treated with all doses of ofatumumab compared to subjects treated with placebo [p < 0.001]. For the primary endpoint, analysis of data from weeks 0-12 estimated a 65% reduction in the cumulative number of new T1 gadolinium enhancing lesions for all doses [p < 0.001]. In weeks 4-12, analyses of data estimated a >= 90% reduction in the cumulative number of new T1 gadolinium enhancing lesions for all cumulative doses of ofatumumab >= 30 mg [p < 0.001].
There were no unexpected safety findings in the study. From weeks 0-12, injection related reactions were the most common adverse reaction and were observed in 52% of subjects receiving ofatumumab compared to 15% of subjects receiving placebo. There were five serious adverse events (SAEs) reported, all subjects received a 60 mg dose of ofatumumab and none of these subjects withdrew from the study. Twelve subjects withdrew during this time period; 10 of these subjects were receiving ofatumumab. To date, no cases of progressive multifocal leukoencephalopathy (PML) or opportunistic infections have been observed.
"We are encouraged by the results from this study, which we believe underline the potential of subcutaneous ofatumumab for treatment of relapsing-remitting multiple sclerosis," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
About the study
This multi-center, randomized, double-blind, placebo controlled Phase II study, conducted by GlaxoSmithKline (GSK), included subjects who had RRMS. The primary objective of the study was to determine whether 3, 30 or 60 mg of ofatumumab given subcutaneously reduces the number of new T1-weighted gadolinium-enhancing brain lesions (active brain lesions) over a period of 12 weeks, as compared with placebo, in subjects with RRMS.
Subjects in the study were randomized to one of the following treatment arms: 3 mg, 30 mg, or 60 mg of subcutaneous ofatumumab every 12 weeks or 60 mg of subcutaneous ofatumumab every 4 weeks, or placebo followed by 3 mg of subcutaneous ofatumumab at week 12. The treatment period for all subjects was 24 weeks; subjects were then followed until B-cell repletion for at least an additional 24 weeks. Currently, all subjects have completed the 24-week treatment period; some subjects continue to be followed as per protocol.
Ofatumumab is a human monoclonal antibody which targets an epitope on the CD20 molecule encompassing parts of the small and large extracellular loopsi. Ofatumumab is being developed under a co-development and collaboration agreement between Genmab and GSK. Under the companies' agreement, GSK is solely responsible for development of ofatumumab in autoimmune indications and all related costs.
Source: The Wall Street Journal Copyright ©2013 Dow Jones & Company, Inc (11/10/13)
With the recent approvals of several oral drugs to reduce disease flares in relapsing-remitting multiple sclerosis, the top researchers agree that the next major frontier is the disease's progressive forms.
But, on the basis of presentations and discussions at last week's annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), progressive MS now stands at about the same place that relapsing-remitting MS stood 3 decades ago -- that is, still many years away from an effective therapy or even a solid understanding of its pathophysiology.
At an ECTRIMS session devoted to progressive MS, opening speaker Robert Fox, MD, of the Cleveland Clinic in Ohio, said an international collaboration has been formed to take on the condition's challenges. Initial meetings have produced a list of five major research needs.
That list highlights how far the field needs to advance before it can even test a potential therapy properly. Currently lacking, but necessary for development of treatments, are the following:
An experimental model for preclinical research
High-throughput screening tools for drug discovery
Appropriate outcome measures for phase II trials
Appropriate outcome measures for phase III trials
Outcomes to target for symptomatic treatments
Fox was followed to the platform by Finn Sellebjerg, MD, of the University of Copenhagen (the meeting's host city), who delved into the heterogeneity of progressive MS. This goes beyond the familiar distinction between primary and secondary progressive forms, to include what is sometimes called progressive-relapsing MS, in which periodic disease flares are superimposed on a background of steadily worsening symptom severity and disability.
Sellebjerg also argued that progressive MS may, in some cases, be a misnomer -- in many patients, their disease course may better be characterized as "incomplete remission after relapse" rather than true progression.
Other speakers in the session discussed different aspects of progressive versus relapsing-remitting forms, such as measures of axonal damage, cerebrospinal fluid protein levels, and variant genes for NMDA (N-methyl-D-aspartate) neurotransmitter receptors.
But none of these appeared to be foolproof approaches to distinguishing the different forms of MS clinically, let alone offering therapeutic targets for drug development.
On the other hand, Fox and Sellebjerg noted that a host of drugs are now or soon will be in clinical trials for progressive MS, because preclinical tests or findings in other neurodegenerative diseases suggested a potential for benefit.
These include simvastatin (Zocor), natalizumab (Tysabri), and alemtuzumab (Lemtrada), as well as a combination of ibudilast, amiloride, and riluzole. This last drug failed in a monotherapy trial in relapsing MS reported at the meeting. On the other hand, drugs for relapsing MS have mostly failed to show benefit in progressive forms, and it would not be surprising if the reverse were true, since the conditions are believed to be fundamentally different.
Sellebjerg said results from a pilot study of natalizumab, in which he had been an investigator, would be reported soon. The topline finding was that the drug showed positive effects in some measures, but brain atrophy continued. Also, although the drug appeared to improve disability scores, Sellebjerg called the magnitude "clinically questionable."
Source: MedPage Today © 2013 MedPage Today, LLC (11/10/13)
Scientists at The Scripps Research Institute (TSRI) have identified a set of compounds that may be used to treat multiple sclerosis (MS) in a new way. Unlike existing MS therapies that suppress the immune system, the compounds boost a population of progenitor cells that can in turn repair MS-damaged nerve fibres.
One of the newly identified compounds, a Parkinson's disease drug called benztropine, was highly effective in treating a standard model of MS in mice, both alone and in combination with existing MS therapies.
"We're excited about these results, and are now considering how to design an initial clinical trial," said Luke L. Lairson, an assistant professor of Chemistry at TSRI and senior author of the study, which is reported online in Nature on October 9, 2013.
Lairson cautioned that benztropine is a drug with dose-related adverse side effects, and has yet to be proven effective at a safe dose in human MS patients. "People shouldn't start using it off-label for MS," he said.
A New Approach
An autoimmune disease of the brain and spinal cord, MS currently affects more than half a million people in North America and Europe, and more than two million worldwide. Its precise triggers are unknown, but certain infections and a lack of vitamin D are thought to be risk factors. The disease is much more common among those of Northern European heritage, and occurs about twice as often in women as in men.
In MS, immune cells known as T cells infiltrate the upper spinal cord and brain, causing inflammation and ultimately the loss of an insulating coating called myelin on some nerve fibers. As nerve fibers lose this myelin coating, they lose their ability to transmit signals efficiently, and in time may begin to degenerate. The resulting symptoms, which commonly occur in a stop-start, "relapsing-remitting" pattern, may include limb weakness, numbness and tingling, fatigue, vision problems, slurred speech, memory difficulties and depression, among other problems.
Current therapies, such as interferon beta, aim to suppress the immune attack that de-myelinates nerve fibers. But they are only partially effective and are apt to have significant adverse side effects.
In the new study, Lairson and his colleagues decided to try a complementary approach, aimed at restoring a population of progenitor cells called oligodendrocytes. These cells normally keep the myelin sheaths of nerve fibers in good repair and in principle could fix these coatings after MS damages them. But oligodendrocyte numbers decline sharply in MS, due to a still-mysterious problem with the stem-like precursor cells that produce them. "Oligodendrocyte precursor cells (OPCs) are present during progressive phases of MS, but for unknown reasons don't mature into functional oligodendrocytes," Lairson said.
A 100,000-Molecule Screen
Using a sophisticated small-molecule screening laboratory that TSRI manages in conjunction with the California Institute of Regenerative Medicine and in collaboration with the California Institute for Biomedical Research (Calibr), Lairson and his team screened a library of about 100,000 diverse compounds for any that could potently induce OPCs to mature or "differentiate."
Several compounds scored well as OPC differentiation-inducers. Most were compounds of unknown activity —but one, benztropine, had been well characterized and indeed was already FDA-approved for treating Parkinson's disease. "That was a surprise, and it meant that we could move forward relatively quickly in testing it," said graduate student Vishal A. Deshmukh, first author of the paper who performed most of these experiments.
With the help of Brian R. Lawson, a senior author of the paper and assistant professor of immunology at TSRI, and his colleague Research Associate Virginie Tardif, Deshmukh set up tests of benztropine in mice with an induced MS-like autoimmune disease—a model commonly used for testing prospective MS drugs.
In these tests, benztropine showed a powerful ability to prevent autoimmune disease and also was effective in treating it after symptoms had arisen—virtually eliminating the disease's ability to relapse. Although benztropine on its own worked about as well as existing treatments, it also showed a remarkable ability to complement these existing treatments, in particular two first-line immune-suppressant therapies, interferon-beta and fingolimod.
"Adding even a suboptimal level of benztropine effectively allowed us, for example, to cut the dose of fingolimod by 90%—and achieve the same disease-modifying effect as a normal dose of fingolimod," said Lawson. "In a clinical setting that dose-lowering could translate into a big reduction in fingolimod's potentially serious side effects." In further analyses, the researchers confirmed that benztropine works against disease in this mouse model by boosting the population of mature oligodendrocytes, which in turn restore the myelin sheaths of damaged nerves—even as the immune attack continues. "The benztropine-treated mice showed no change in the usual signs of inflammation, yet their myelin was mostly intact, suggesting that it was probably being repaired as rapidly as it was being destroyed," said Lawson.
Benztropine is known to have multiple specific effects on brain cells, including the blocking of activity at acetylcholine and histamine receptors and a boosting of activity at dopamine receptors. But Lairson and his colleagues found evidence that the drug stimulates OPCs to differentiate mainly by blocking M1 or M3 acetylcholine receptors on these cells.
In addition to setting up initial clinical trials, Lairson and his team hope to learn more about how benztropine induces OPC maturation, and how its molecular structure might be optimized for this purpose. "We're also looking at some of the other, relatively unknown molecules that we identified in our initial screen, to see if any of those has better clinical potential than benztropine," he said.
"This work, like our previous studies with hematopoietic and mesenchymal stem cells, illustrates the power of small molecules to control stem and precursor cells in ways that may ultimately lead to a new generation of drugs for regenerative medicine," said Peter G. Schultz, the Scripps Family Chair Professor in the Department of Chemistry at TSRI and one of the study's senior authors.
Source: News-Medical.Net (10/10/13)
Scottish Medicines Consortium approves botulinum toxin type a (Botox) for MS bladder symptoms(10/10/13)
Botulinum toxin type a (Botox) has been approved for the management of urinary incontinence in adult patients with neurogenic detrusor overactivity due to subcervical spinal cord injury (traumatic or non-traumatic) or multiple sclerosis, who are not adequately managed with anticholinergics; patients should be already catheterising or willing and able to catheterise if required.
How does it work?
Botulinum toxin type A blocks a chemical used in nerve communication called acetylcholine, which causes detrusor smooth muscle to be paralysed, and also changes bladder reflexes. Botulinum toxin type A is given by injection into the muscle of the bladder. Repeat injections should not be given within 3 months.
What has SMC advised?
SMC has accepted botulinum toxin type A for the management of urinary incontinence in adult patients with neurogenic detrusor overactivity due to subcervical SCI (traumatic or non-traumatic) or MS, who are not adequately managed with anticholinergics. Patients should be already catheterising, or willing and able to catheterise if required.
What is the evidence for this?
Two studies in which all patients received best supportive care showed that botulinum toxin type A significantly reduced weekly urinary incontinence episodes over a 6-week period compared with placebo (a dummy treatment containing no active ingredient). There are currently limited data on re-treatment.
An economic analysis compared botulinum toxin type A and best supportive care with best supportive care alone which included behavioural therapy, incontinence pads (alone or in combination with catheterisation) and anticholinergic medicines. Despite a number of uncertainties, the medicine was considered to offer value for money.
SMC accepted botulinum toxin type A for use because the balance of costs and benefits meant that it was considered to offer value for money. Due to the limited treatment options beyond best supportive care for patients who are not adequately managed with anticholinergics, there is an unmet need in this patient group.
Find out more about MS Urinary symptoms in our Choices leaflet.
Source: Scottish Medicines Consortium (10/10/13)
Multiple sclerosis is an inflammatory disease in which the immune system attacks the nervous system. The result can be a wide range of debilitating motor, physical and mental problems. No one knows why people get the disease or how to treat it.
In a new study published in the Journal of Neuroimmune Pharmacology, Ewa Kozela, Ana Juknat, Neta Rimmerman and Zvi Vogel of Tel Aviv Univ.'s Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases and Sackler Faculty of Medicine demonstrate that some chemical compounds found in marijuana can help treat MS-like diseases in mice by preventing inflammation in the brain and spinal cord.
"Inflammation is part of the body's natural immune response, but in cases like MS it gets out of hand," says Kozela. "Our study looks at how compounds isolated from marijuana can be used to regulate inflammation to protect the nervous system and its functions." Researchers from the Weizmann Institute of Science co-authored the study.
Israel has a strong tradition of marijuana research. Israeli scientists Raphael Mechoulam and Yechiel Gaoni discovered THC, or tetrahydrocannabinol, in 1964, kick-starting the scientific study of the plant and its chemical constituents around the world. Since then, scientists have identified about 70 compounds — called cannabinoids — that are unique to cannabis and have interesting biological effects. In the 1990s, Prof. Vogel was among the first researchers to describe endocannabinoids, molecules that act like THC in the body.
Besides THC, the most plentiful and potent cannabinoid in marijuana is cannabidiol, or CBD. The TAU researchers are particularly interested in CBD, because it offers medicinal benefits without the controversial mind-altering effects of THC.
In a 2011 study, they showed that CBD helps treat MS-like symptoms in mice by preventing immune cells in their bodies from transforming and attacking the insulating covers of nerve cells in the spinal cord. After inducing an MS-like condition in mice — partially paralyzing their limbs — the researchers injected them with CBD. The mice responded by regaining movement, first twitching their tails and then beginning to walk without a limp. The researchers noted that the mice treated with CBD had much less inflammation in the spinal cord than their untreated counterparts.
High hopes for humans
In the latest study, the researchers set out to see if the known anti-inflammatory properties of CBD and THC could also be applied to the treatment of inflammation associated with MS — and if so, how. This time they turned to the immune system.
The researchers took immune cells isolated from paralyzed mice that specifically target and harm the brain and spinal cord, and treated them with either CBD or THC. In both cases, the immune cells produced fewer inflammatory molecules, particularly one called interleukin 17, or IL-17, which is strongly associated with MS and very harmful to nerve cells and their insulating covers. The researchers concluded that the presence of CBD or THC restrains the immune cells from triggering the production of inflammatory molecules and limits the molecules' ability to reach and damage the brain and spinal cord.
Further research is needed to prove the effectiveness of cannabinoids in treating MS in humans, but there are reasons for hope, the researchers say. In many countries, CBD and THC are already prescribed for the treatment of MS symptoms, including pain and muscle stiffness.
"When used wisely, cannabis has huge potential," says Kozela, who previously studied opiates like morphine, derived from the poppy plant. "We're just beginning to understand how it works."
Source: Advantage Business Media © Copyright 2013 Advantage Business Media (09/10/13)
Researchers in Spain have identified lipid-specific antibody bands in the cerebrospinal fluid (CSF) that are associated with an aggressive presentation of multiple sclerosis (MS), and patients with these antibodies seem to have a much lower risk for progressive multifocal leukoencephalopathy (PML) with natalizumab therapy (Tysabri, Biogen Idec).
"The presence of lipid-specific IgM bands in the CSF signals patients with aggressive disease and highly activated immune systems," said Luisa Villar, PhD, Hospital Ramón y Cajal, Madrid, Spain. "We seem to be able to lower the immune system in patients in whom it is highly activated without inducing immunosuppression. So natalizumab is safe to use in this population, and these are the very patients who need this strong drug.
"About one third of MS patients test positive for IgG antibodies," she added. "These patients generally have highly active disease, with many relapses. Beta-interferons don't work well for these patients and so they need a stronger drug right from the start. Therefore natalizumab is a good treatment option for these patients," Dr. Villar told Medscape Medical News. "And now we have shown that natalizumab is actually very safe in this group too. Our cohort of patients, some of whom have been treated for 5 years, have an extremely low risk of developing PML."
Dr. Villar says her hospital now routinely tests for IgM in all new patients with MS. "If positive, I would recommend natalizumab as first-line therapy. I am trying to urge other hospitals in Spain to do the same."
She explained that the IgM antibodies are targeted against lipids and they recognize myelin in the axons of neurons, which is extremely rich in lipids.
Dr. Villar presented their findings at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
In her presentation, Dr. Villar noted that IgM antibodies are believed to have a role in the pathology of MS. "Most patients with IgM bands in the CSF show suboptimal response to beta-interferon, but a good response to natalizumab, with 90% of inhibition of relapse rate and stabilization or improvement of EDSS [Expanded Disability Status Scale] score in most cases."
The aim of the current study was to explore the risk for PML in patients with and without these IgM antibody bands. The study involved 365 patients treated with natalizumab, of whom 240 tested positive for IgM. There were 22 cases of PML reported.
Results showed that IgM antibodies were detected in 70% of patients in the group who did not get PML but in only 1 (4%) of those who did get PML.
"We now have data on 365 patients on natalizumab," she said. "Of these, 240 are positive for IgM and in this group there has only been 1 case of PML. In the 120 patients who are IgM negative there were 21 cases of PML. These data are absolutely significant."
She added that patients who developed PML had a much longer disease duration when they started natalizumab therapy, but the duration of natalizumab treatment in both groups was similar.
Upon analysis of JC virus (JCV) antibody status (the virus that causes PML), about half the patients who did not develop PML and all but 1 patient who developed PML were found to be JCV positive.
Dr. Villar reported that the presence of IgM antibodies lowered the risk for PML in patients positive for JCV antibodies to that of patients who tested negative for JCV antibodies.
When asked for a possible explanation of these observations, Dr. Villar noted that patients who test positive for IgM antibodies also have very high levels of CD4 lymphocytes.
"They have highly inflammatory disease, with 20 times more CD4 lymphocytes than IgM-negative patients before treatment with natalizumab." She suggested that in patients with such highly inflammatory disease, the immune system is so activated that the patient is protected against the development of immunosuppression with natalizumab.
Dr. Villar has received speaking honoraria from Bayer Schering Pharma, Merck Serono, Biogen-Idec, Teva Pharmaceuticals, sanofi-aventis, and Novartis.
29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Abstract 180. Presented October 4, 2013.
Source: Medscape Copyright © 1994-2013 by WebMD LLC (09/10/13)
A study published in the British medical journal The Lancet finds that narrowing of the veins leading from the brain -- a condition called CCSVI -- is just as prevalent in patients with Multiple Sclerosis as in people without the disease.
The study, funded by the MS Society of Canada and led by Dr. Anthony Traboulsee of the University of British Columbia, calls into question the controversial theory that MS is caused by or associated with CCSVI, or chronic cerebrospinal venous insufficiency.
Four years ago, Italian doctor Paolo Zamboni proposed that MS was linked to constricted veins in the head and neck. He provided research that showed that opening the veins with tiny balloons – a procedure he dubbed the liberation treatment -- could improve symptoms in patients and reduce the number of attacks. Since then, hundreds of patients have sought the procedure and dozens of studies have been presented -- all with conflicting results.
The Lancet study used ultrasound to examine the veins of 79 people with MS, as well as a procedure called catheter venography. They also looked at the veins of 55 people who were siblingsof the patients, as well as 43 unrelated healthy volunteers.
Traboulsee, an associate professor of Neurology at UBC and director of the MS Clinic at UBC Hospital, says that catheter venography is considered the most accurate, "gold standard" technology for revealing the size and shape of veins. The procedure involves injecting a dye into a vein and then examining the vein through an X-ray.
The research team compared the width of veins between the brain and the heart with a normal reference point taken from below the jaw.
They say they found that at least two-thirds of the 79 MS patients and the two groups of healthy volunteers had veins that narrowed by at least 50 per cent. The differences in rates of venous narrowing between the groups were not statistically significant.
In all, vein narrowing was present in:
74 per cent of people with MS
66 per cent of their unaffected siblings
70 per cent of the unrelated volunteers
“It’s certainly clear now that the CCSVI or these narrowings are not the cause of Multiple Sclerosis. They’re just too common to be the cause of Multiple Sclerosis,” Traboulsee said during a news conference Tuesday.
He said the study also showed that the ultrasound criteria usually used to diagnose CCSVI are unreliable. Ultrasound found vein narrowing in fewer than half the cases that were detected by catheter venography.
“We think this is going to be very important information for patients and families, to say look at all the different studies out there when trying to make decisions about their care,” he said.
But MS patient Steve Garvie says the study raises some important questions in his mind – namely, why does he feel so much better after getting the liberation treatment for himself?
“This does work, and it does give people their lives back,” Garvie told CTV News. “I think that every single person should have blood flowing in their body properly, whether they have MS or not.”
Garvie says he worries the study will stop other MS patients from undergoing liberation treatment. “They will dwell in pain and suffer let MS run its course, unfortunately.” Dr. Sandy McDonald, a vascular surgeon based in Barrie, Ont., said the new study hasn’t added any clarity to an important question: Does CCSVI provide any benefit to those with MS?
“We don’t know if the quality of life is better; that trial is yet to be done.”
Still, two MS experts who reviewed The Lancet study, Dr. Friedemann Paul of Germany and Dr. Mike Wattjes of the Netherlands, write in an accompanying commentary that the results sound a "death knell" for the CCSVI hypothesis.
"If chronic cerebrospinal venous insufficiency actually existed, the ultrasound findings of this study and previous studies would suggest that up to half of the general and otherwise healthy population should be judged to be seriously ill because of venous insufficiency of the cervical veins," they write.
For his part, Traboulsee is still working on a study on the effectiveness of the so-called “liberation therapy."
His team is providing angioplasty to MS patients with narrowed neck veins as well as sham (placebo) treatments. Each group will then "cross over" to the other treatment after a year, so that all patients will receive the angioplasty at some point. Results from that study are expected in late 2015.
Traboulsee says many MS patients want to know if the liberation procedure is beneficial.
"We are committed to evaluating this treatment with robust methods and utilizing patient-focused outcomes," he says.
Source: CTV News © 2013 Bell Media (09/10/13)
Biogen Idec Inc. said its new multiple-sclerosis drug, Tecfidera, wasn't to blame for the death earlier this year of a 59-year-old woman who had taken the pill.
In July, the Weston, Mass., biotech company said it was investigating the death of the woman from a form of pneumonia that the company said was common in multiple-sclerosis patients. She had taken Tecfidera for 5½ weeks before vomiting, diarrhea and other side effects prompted her to stop taking the pill, and died 2½ weeks after discontinuing treatment, the company had said. The woman had a history of irritable bowel disease and recurring infections like bronchitis, according to the company.
A Biogen spokeswoman said Monday that the physician who treated the woman concluded that Tecfidera wasn't the cause and that the company agreed with the assessment. "The case has been assessed and it was determined that the death was unrelated to Tecfidera," the spokeswoman said. Biogen has declined to identify the woman.
Tecfidera was approved in March to treat patients suffering from periodic attacks of multiple sclerosis, a painful neurological condition in which the immune system damages healthy nerves and disrupts brain signals.
Early sales for the pill have been strong, and some analysts expect it could eventually notch more than $4 billion in yearly world-wide revenue. In the second quarter of this year, Tecfidera generated $192 million of Biogen Idec's $1.4 billion revenues.
The drug is up for approval in the European Union.
During testing, the most common side effects were flushing, as well as nausea, vomiting and diarrhea, especially at the start of treatment, according to the U.S. Food and Drug Administration. Another risk, the agency said, was a decrease in the count of white blood cells that help fight off infections, though there wasn't a significant increase in infections among study subjects taking Tecfidera.
Last week, Biogen presented data at a medical meeting in Copenhagen showing "no new or worsening safety signals," such as a higher risk of serious infections, in study subjects who had been taking the drug for up to 6½ years.
Source: The Wall Street Journal Copyright ©2013 Dow Jones & Company, Inc (08/10/13)
A blood test for L-selectin expression on circulating immune cells may identify multiple sclerosis patients who could safely receive natalizumab (Tysabri) despite past exposure to the JC virus, a small study presented here suggested.
All MS patients taking natalizumab who developed the rare but life-threatening brain inflammation called progressive multifocal leukoencephalopathy (PML) in the study had very low levels of L-selectin expression, which was not seen in other patients who did not develop PML or in controls, said Heinz Wiendl, MD, of the University of Muenster in Germany.
He and his colleagues at the Muenster MS clinic have begun to implement the test in patients, he told attendees at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting, using a cutoff of 30% of circulating T cells positive for L-selectin (also known as CD62L).
So far, 10 patients had levels consistently below the cutoff in repeat testing. Four stopped natalizumab after counseling, Wiendl said. One developed PML, and five others are still taking the drug but with no sign of PML so far.
A larger validating study is now underway, with 342 patients accrued so far, Wiendl said.
PML results from reactivation of latent infection with the JC virus, which is common in the general population. It has been a particular problem with natalizumab, appearing shortly after the drug was approved in 2004 and forcing it off the U.S. market until its manufacturer implemented a strict risk evaluation and mitigation strategy.
Current recommendations call for JC virus serological testing in patients prior to starting natalizumab and periodically while on the drug to detect new infections. Although a positive test is not an absolute contraindication for the drug -- it remains the standard of care for patients showing aggressive MS activity in patients taking first-line therapies -- it is to be prescribed cautiously.
PML risk in patients with JC virus infection is increased with prior immunosuppressive therapy and duration of natalizumab treatment beyond 2 years.
Natalizumab mainly targets the alpha-4 integrin protein, an adhesion molecule, as is L-selectin. Studies of T cells in blood and cerebrospinal fluid (CSF) taken from 381 patients treated at the Muenster clinics showed that alpha-4 integrin expression in CSF T cells was essentially nil in natalizumab-treated patients.
But because some type of adhesion molecule action is necessary for T cells to enter CSF, Wiendl said, the finding indicated that an alternative pathway must exist, prompting the attention to L-selectin.
Among patients with long-term natalizumab therapy who did not develop PML, a mean of 40.2% of their peripheral blood CD4-positive T cells expressed L-selectin, whereas in the eight patients who later developed PML and for whom pre-PML blood samples were available, the average was 4.6% (P<0.0001), Wiendl said.
He told MedPage Today that the most obvious use of an L-selectin test would be to identify patients with past JC virus exposure on natalizumab with relatively high T-cell expression of L-selectin, since so far they appear to be at low risk for PML.
But he noted that JC virus-negative patients could benefit as well, because their risk of PML is not zero. JC virus serology tests may miss patients with recent infection or may simply be wrong; and the condition can be caused by other viruses.
Currently, he said, the group is beginning to test patients when they have received 18 natalizumab infusions, and then every 6 months. (He said the test "is very laborious.") In patients with L-selectin positivity in less than 30% of CD4-positive T cells, a switch to other therapies is considered.
Session co-moderator Fred Lublin, MD, of Mount Sinai School of Medicine in New York City, told MedPage Today that it was too early to say how much promise the technology held. "Not enough data," he said.
Wiendl agreed, even though his clinic is already using the test to help guide treatment management in patients. "We need four-digit numbers [of patients] to really validate it."
The study had no commercial funding.
Wiendl reported relationships with Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, Teva, and Novo Nordisk.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Schneider T, et al "Dynamic biomarkers for clinical efficacy and individual PML prevention under natalizumab therapy" ECTRIMS 2013; Abstract 232.
Source: MedPage Today © 2013 MedPage Today, LLC (08/10/13)
ALS drug fails as treatment for early MS(08/10/13)
Riluzole (Rilutek), a drug used in treatment of patients with amyotrophic lateral sclerosis, did not help prevent brain matter loss in early relapsing/remitting multiple sclerosis, researchers reported here.
After adjustment for key differences in the randomization process, Emmanuelle Waubant, MD, assistant professor of neurology at the University of California San Francisco, said that treatment with riluzole resulted in a decrease in brain volume by 0.26% a year compared with placebo treatment (difference of -0.26, 95% CI -0.057 to 0.014, P=0.22).
In a late-breaker oral report at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, Waubant said that in the unadjusted analyses, "Brain volume in the placebo group decreased at a rate of 0.49% per year whereas the active group decreased at 0.86% a year, so there was a 0.37% more brain volume decrease in the riluzole group (difference of -0.37, 95% CI -0.78 to 0.024, P=0.065)."
In addition, brain volume decrease greater than 2% per patient over the 36-month course of the trial occurred in seven patients on riluzole compared with one patient on placebo, she said. The primary endpoint of the study was percent brain volume change as measured by Structural Image Evaluation, using Normalization, of Atrophy (SIENA) protocols.
Waubant, when questioned by an audience member about whether the drug might have had a detrimental impact on the patients, suggested that because of the small number of patients in the study and a number of inequities in the randomization process, the statistical adjustments appeared to attenuate the differences in outcome.
In the trial, the 22 patients who were randomly assigned to riluzole were older -- 38.2 years versus 32.4 years for the 21 patients assigned to placebo (P=0.042). She also noted that the riluzole patients at baseline had less normalized grey matter volume and less normal-appearing white brain matter volume than placebo patients, although the differences were not statistically significant. The riluzole group also had more normalized lesion volume at baseline than placebo patients, but again, this was not a statistically significant difference.
"With a small study it is difficult to use too many variables in performing statistical adjustments," she acknowledged, but she said her overall impression was that there were minimal differences between treatment with riluzole or with placebo.
"We saw no effect of riluzole that we could detect in early relapsing/remitting multiple sclerosis on clinical and imaging outcome measures," she concluded. "We can't rule out that there was an effect, but our study may have been too small and too short to detect that effect. However, the 95% confidence interval suggests that if a true treatment effect was present but missed due to small numbers or time, that effect would be mild."
In the trial, Waubant and her colleagues recruited patients with clinically isolated syndrome or early state relapsing/remitting multiple sclerosis and assigned all of them to 4 weeks of riluzole to determine tolerability to the drug. They were then assigned to either riluzole or placebo, in addition to treatment with interferon beta-1b.
Adult patients up to age 55 were included in the trial. They had to be naive to interferon treatments and had to have been off glatiramer acetate therapy for at least 6 months to be eligible for the study. Waubant reported that 20 patients on riluzole completed the 24-month core study, and nine completed the 36-month study. She said 18 patients on placebo completed the core study and 13 completed 36 months. The analysis, however, was based on intention to treat of all 43 patients who were randomized.
This research was performed as a research grant funded by the National MS Society.
The trial received support in the form of free medications and placebo from sanofi and Biogen-Idec.
Waubant disclosed commercial relationships with Roche, sanofi, Genentech and Novartis. Other co-authors disclosed commercial interests with Hoffmann-La Roche, Biogen-Idec, and Genzyme.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Waubant E, et al "A phase II trial of neuroprotection with riluzole in early relapsing-remitting MS" ECTRIMS 2013, Abstract 234.
Source: MedPage Today © 2013 MedPage Today, LLC (08/10/13)
Teva Pharmaceutical Industries Ltd. announced further results from a long-term, open-label extension study of glatiramer acetate (GA). The extension study was designed to evaluate the long-term neurologic disease course, and the safety and efficacy of glatiramer acetate 20 mg daily, the therapeutic agent in Copaxone(R) (glatiramer acetate injection), which is indicated for reduction of the frequency of relapses in patients with relapsing-remitting multiple sclerosis (RRMS). Detailed study results will be presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark during poster session P577 on October 3, 2013.
"To our knowledge, glatiramer acetate is the only treatment for multiple sclerosis that has been prospectively studied for nearly two decades in a continuously monitored, long-term study," said Dr. Michael Hayden, President of Global R&D and Chief Scientific Officer for Teva Pharmaceutical Industries Ltd.
In this analysis of 74 patients, the cumulative annualized relapse rate (ARR) over the study period was 0.2, with 24.3 percent of patients remaining relapse-free through the entire observation period. Additionally, 63.3 percent of enrolled patients stayed below EDSS 4, while 79.5 percent stayed below EDSS 6 throughout the course of the study. Advancement to secondary progressive MS (SPMS), defined by a greater than 1.0-point EDSS progression (or greater than 0.5 for patients with baseline scores greater than 6) sustained for greater than or equal to 12 months without relapse, was seen in 35 patients (47 percent). Adverse events (AEs) leading to study discontinuation with incidence greater than one percent over the 20-year observation period were largely related to site reactions, while incidence of serious AEs were notably low, with no unexpected findings.
About the open-label extension study
The open-label extension study is a long-term clinical analysis of patients that participated in the original 36-month, randomized placebo-controlled U.S. Glatiramer Acetate Trial. The objective of the extension study was to evaluate the long-term neurologic disease course, and the safety and efficacy of glatiramer acetate 20 mg daily, in patients with relapsing-remitting multiple sclerosis. Ongoing patients in this study were continuously treated with glatiramer acetate 20 mg daily for a mean of 19.3 years (SD=1.3, range 18-21) with an average disease duration of 27.3 years. Baseline assessments for each patient in this pooled analysis were taken at the start of GA therapy.
Source: Teva Pharmaceutical Industries Ltd (08/10/13)
Patients with multiple sclerosis and other neurological diseases are to benefit from a research clinic that will be officially opened later.
The Anne Rowling Regenerative Neurology Clinic at the University of Edinburgh is to be opened by Her Royal Highness, The Princess Royal.
The centre will look at finding treatments to slow progression of neurodegenerative diseases.
It was established with a donation from Harry Potter author JK Rowling.
It is named after the author's mother, who had the disease and died aged 45.
The centre will look at conditions such as multiple sclerosis, motor neurone disease, Huntington's disease and Parkinson's disease, as well as autism and early-onset Alzheimer's disease.
The Princess Royal, who is Chancellor of Edinburgh University, will be given a tour of the clinic and staff and students will demonstrate the facilities and describe current research projects.
Ms Rowling, who donated £10m, said: "I am moved and elated to see the Anne Rowling Clinic formally opened today by HRH The Princess Royal.
"Having observed the plans for the clinic develop and expand to fulfil the needs of patients, clinicians and researchers, I am now very proud to see the building finished and operating as the beating heart of this centre for excellence.
"Thank you to everyone who has been involved in its creation and operation."
Prof Siddharthan Chandran, professor of neurology and co-director of the clinic, said: "We are delighted to officially open this clinic.
"All patients with these tough diseases need treatments that will slow, stop and ideally reverse damage.
"The Anne Rowling Clinic will pioneer discovery science and innovative clinical research through strong partnerships with the NHS, academia and industry around the world.
"Only by better understanding the biological processes behind these devastating diseases can we identify new targets for potential therapies and take them into clinical trials."
Source: BBC News © British Broadcasting Corporation 2013 (08/10/13)
A new UK study has revealed that people with MS do not always report their relapses despite the domino effect on their health, financial security and support networks. The study also uncovered that inadequate patient reporting of relapses may bias views of clinicians on the adequacy of disease modifying treatments. Preliminary findings from the study presented at the 29th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) have shown a worrying trend towards MS health professionals accepting a level of ongoing MS relapses as inevitable without considering alternative treatments, as well as significant underreporting of relapses by patients. Nearly half (46%) of respondents had experienced a relapse but did not report it.
The Novartis funded MS Pathways study led by Dr Martin Duddy, consultant neurologist at Royal Victoria Infirmary, Newcastle found that over a quarter of people had not reported their most recent relapse, despite two out of three employed respondents having to take time off work and 66% needing to call on their support network for help with simple daily tasks. The financial burden of relapses was striking, with a third of respondents reporting a reduction in family income, nearly half (48%) of respondents had to temporarily reduce their hours, whilst 8% had to permanently reduce their hours and 10% had to give up work entirely.
Dr Martin Duddy commented; "Even minor relapses have an impact on a patient's physical and psychological well being, as well as their financial well being. The uncertainty of not knowing when the next relapse might come can be a strain for many people. We need to have a clear picture of whether or not patients are having relapses, as they have an important role in assessing whether they need treatment and whether that treatment is working."
The main reasons cited for underreporting were that patients considered their symptoms too mild or did not feel there was anything healthcare professionals could do.
Over the past few years clinical opinion regarding relapses has begun to change, with a clear shift away from unquestioning acceptance of relapses, towards all relapses being considered a sign of clinical activity that merit discussion and action. The MS Pathways study provides further evidence to support the need for better systems to ensure full reporting of relapses so that MS healthcare professionals can make informed treatment decisions with their patients.
Amy Bowen, Director of Service Development at the MS Trust commented; "The MS Trust welcomes this important study. It is crucial that we improve reporting of relapses and ensure that people with MS receive the right information about recognising a relapse and the treatment that is available to help them manage its impact. No one should be coping with the burden and disruption of a relapse without the support of their MS team, particularly their MS specialist nurse."
MS is the most common neurological condition affecting young adults in the UK. It is estimated that over 100,000 people in the UK have MS - relapsing remitting MS (RRMS) is the most common form, affecting 80% of people.
Relapses are unexpected and can happen at any time. The impact of a relapse can last for weeks or months and the symptoms may range from loss of vision to spasm and mobility problems. Such symptoms can have a huge impact on family life, work and social activities, and the unpredictable nature of relapses can make it difficult for a person with MS to plan ahead with confidence.
The number of relapses experienced (annualised relapse rate) is one of four key measures used to assess the progression of a patient's MS, in addition to physical disability, lesion activity on MRI and brain volume loss as measured by MRI.
A team of MS healthcare professionals, including Dr Duddy are working together with Novartis to develop educational materials to support more effective reporting of relapses.
Source: Medical News Today © 2004-2013 MediLexicon International Ltd (08/10/13)
Dietary salt associated with MS activity(07/10/13)
Sodium intake was positively correlated with risk of increased disease activity in patients with multiple sclerosis, according to a small study reported here.
Each gram of estimated daily sodium intake above the average in a 52-patient sample was associated with an increase of 3.65 in MRI lesion counts, said Mauricio Farez, MD, PhD, of Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia in Buenos Aires.
Also, patients with estimated salt intake classified as high -- more than 4.8 g daily -- showed relapse rates that were 3.95 times greater (95% CI 1.39-11.21) than those with intakes less than 2 g/day, he told attendees at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.
Farez emphasized repeatedly that the findings did not prove that high salt intake caused the increased disease activity. He acknowledged that, if there is a causal relationship, it possibly could go in the reverse direction -- that patients with highly active MS may increase their salt intake as a result. But he said he did not view that as very likely.
The study in a total of 122 patients with relapsing-remitting MS grew out of previous research connecting salt intake with vitamin D levels and body mass index, he said. Numerous studies have indicated an association between vitamin D status and MS risk -- including one reported minutes earlier at the Copenhagen meeting -- and it seemed logical to examine whether sodium may share a similar association, Farez explained.
He and colleagues initially recruited 70 patients for a first phase of the observational study. They underwent a baseline MRI scan in November 2010, followed by MRI scans and analysis of urinary sodium excretion as a means of estimating sodium intake 1 year later. Finally, in November 2013, relapse rates for the preceding 2 years were calculated.
During this first phase, the MRI analyses included "combined unique activity" counts -- the total of new T2 lesions and new gadolinium-enhancing T1 lesions since the baseline scan.
A second group of 52 patients was examined in June 2013 with MRI scans and urinary sodium testing to provide replication data for the association between sodium intake and MRI lesion activity. Because this group had only a single scan and no follow-up, Farez and colleagues could only calculate T2 lesion loads, not the combined unique activity lesion counts nor relapse rates.
Farez acknowledged that an important limitation of the study was that it did not measure urinary sodium excretion with 24-hour urine collections, which he said were impractical since they require participants to carry a large container to capture all their urine for a whole day and night.
Instead, his team relied on spot urine collections and a published formula to estimate daily sodium excretion and, from that, daily sodium intake.
He reported that, in the first group of patients, not only those with high sodium intake (more than 4.8 g/day) but also those with "average" consumption showed increased risk of relapse. Participants with estimated daily intake of 2.0 to 4.8 g/day had relapse rates that were 2.75 times that of the low-intake group (95% CI 1.30-5.81).
Comparing both the average- and high-intake groups, the trend was significant at P=0.001, he reported.
Also in the first group, combined unique activity lesion counts were approximately three times greater in both the average- and high-intake groups compared with the low-intake group (P not reported), Farez said.
And, T2 lesion counts were similar in the first cohort's low- and average-intake groups at an average of about 6, but they reached a mean of approximately 14 in the high-intake group (P<0.05).
In the replication set of 52 patients, similar results were seen, Farez said. He and his colleagues calculated that each increment in intake of 1 g above the cohort average was associated with 3.65-lesion increase in T2 count (SD 0.77, P<0.001).
He did not specify the cohort average, but he said that the national average in Argentina has been measured at nearly 5 g/day, well above the U.S. mean of 3.4 g/day.
The World Health Organization has recommended a maximum daily intake of 2 g/day. In the U.S., several government agencies have jointly called for a maximum of 1.5 g/day -- but earlier this year, the Institute of Medicine complained that the scientific evidence did not a support such a low figure, instead backing an older standard of 2.3 g/day.
Farez and colleagues also measured serum sodium but found no relationship between it and clinical or MRI activity. It was also not significantly associated with estimated sodium intake, with an R2 value of just 0.0082.
Asked by the session moderator what a causal mechanism might be, Farez said previous studies had suggested that high salt levels can promote increased inflammatory activity throughout the body. Also, he said, it may increase permeability in the blood-brain barrier, which could contribute to inflammation in the central nervous system.
Whatever such a mechanism may be, he said, "it does not seem to occur in peripheral blood."
The study had no commercial funding.
Farez reported a relationship with Merck Serono. Other investigators reported relationships with this firm and with Biogen Idec, Novartis, and Teva.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Farez M, et al "Sodium intake is associated with increased disease activity in multiple sclerosis" ECTRIMS 2013; Abstract 119.
Source: MedPage Today © 2013 MedPage Today, LLC (07/10/13)
Patients with secondary progressive multiple sclerosis who were able to stay on cyclophosphamide therapy had a lower risk of further disability, but their dropout rate from treatment was more than twice that for methylprednisolone therapy, researchers reported here.
Of the 72 patients enrolled in the cyclophosphamide arm of the trial, 33 dropped out of treatment before the end of the 2-year study -- 20 of them due to adverse events, reported Bruno Brochet, MD, chief of neurology at the University of Bordeaux Segalen, France.
Even though risk of decline of the Expanded Disability Status Scale score was reduced 58% by treatment with cyclophosphamide, in the intention-to-treat analysis the use of cyclophosphamide failed to reach statistical significance as a superior treatment to methylprednisolone, a standard of care in France, Brochet said in his oral presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
In the primary endpoint analysis, 18.1% of patients treated with cyclophosphamide experienced definite deterioration as measured by the Expanded Disability Status Scale score, compared with 31.8% of the patients taking methylprednisolone (P=0.06), he said.
He illustrated that treatment with cyclophosphamide decreased the risk of deterioration by 58% (95% CI 0.19-0.92), but the hazard ratio of premature end of treatment was 2.56 (95% CI 1.13-5.79).
Among secondary endpoints, Brochet said there were no significant differences in timed walking distances, or in the Multiple Sclerosis Functional Composite, between the two groups.
He said that 76.6% of those on cyclophosphamide were relapse-free after 2 years compared with 56.1% of those on prednisolone, but that again missed statistical significance (P=0.07).
"According to the multi-state model, cyclophosphamide is a risk factor for treatment interruption, but cyclophosphamide is protecting patients who continued their treatment from progression as assessed by the Expanded Disability Status Scale," Brochet said.
"I do not think these results are compelling for use of cyclophosphamide," said Vesna Brinar, MD, professor of neurology at University of Zagreb, Croatia, who moderated the free communications session at ECTRIMS.
"The high dropout rate indicates that this treatment might be useful only in carefully selected patients," she told MedPage Today.
In the study, Brochet and colleagues randomly assigned 72 individuals with secondary progressive multiple sclerosis to cyclophosphamide and 66 similar patients to treatment with methylprednisolone. Brochet, in responding to questions from his audience, said the researchers did not include a placebo group because of the widespread use in France of methylprednisolone as a standard of care in the disease.
"Therapeutic options are very limited in secondary progressive multiple sclerosis," he noted.
He said the researchers in the so-called PROMESS study considered the use of cyclophosphamide as an agent that could reduce inflammation, an ongoing process that is believed to have a role in secondary progressive multiple sclerosis.
Patients at 27 participating centers in France were randomly assigned to either cyclophosphamide or methylprednisolone and were administered intravenous therapy monthly for 1 year, and then every other month for the second year of the trial. Patients were admitted to the trial if they exhibited a phase of gradual progression of disability of at least 6 months, but less than 4 years. The recent deterioration must have been at least a 0.5 worsening score on the Expanded Disability Status Scale score over the past 12 months.
The patients were about 48 years of age; about 65% were women; their average disease duration was around 12 years. Their median Expanded Disability Status Scale score was 5 (eligible patients had to score between 4 and 6.5 on the scale.)
Patients on cyclophosphamide averaged 8.6 adverse events compared with 6.2 adverse events on prednisolone. He said that 70 of 72 patients on cyclophosphamide had at least one adverse event, compared with 61 of 66 patients on prednisolone.
This study was promoted by CHU de Bordeaux and supported by the Programme Hospitalier de Recherche Clinique 2004.
Brochet disclosed commercial relationships with Bayer Pharma, Biogen-Idec, Merck Serono, Genzyme, Novartis, sanofi, Roche and Teva. Co-authors also disclosed commercial relationships with Almirall, Bayer-Schering, Lilly, and Peptimmune.
Brinar had no disclosures.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Brochet B, et al "Double-blind, randomized, controlled study of cyclophosphamide versus methylprednisolone in secondary progressive multiple sclerosis: PROMESS study" ECTRIMS 2013; Abstract 169.
Source: MedPage Today © 2013 MedPage Today, LLC (07/10/13)
Stressful life events in childhood did not appear to increase the subsequent risk for multiple sclerosis (MS), researchers said here.
In large Danish cohort study, children who experienced stressful life events had a weak 1.11-fold risk (95% CI 1.02-1.20) of later developing MS compared to unexposed children, according to Nete Munk Nielsen, MD, PhD, from Statens Serum Institut in Copenhagen, and colleagues.
However, there was a "slightly increased risk of MS" for kids who experience parental divorce (relative risk 1.13, 95% CI 1.04-1.23) compared to children who did not, they wrote in their poster presentation at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.
While stressful events are often associated with risk for MS in adults, studies that have looked for an association between stress and MS in children have turned in mixed results.
The authors pointed out that a recent study found that adults exposed to emotional or sexual abuse as children were at 2.2- to 3.4-fold increased risk of MS. However, another study reported no association between physical or sexual abuse in childhood and risk for MS.
The authors analyzed Danish public health records that included nearly 3 million individuals born between 1968 and 2011. The Danish Civil Registration System contains updated information on family relations, marital status, and vital statistics on every Danish person since April 1, 1968. The researchers compiled data on parental and sibling deaths as well as parental divorce. Information about cases of MS in the study cohort was obtained from the Danish MS Registry.
The cohort represented 63 million person-years of follow-up. The records showed that 15.8% of the population was exposed to at least one stressful life event before the age of 18, with most of those events being parental divorce.
The researchers identified 3,260 individuals in the cohort who were later diagnosed with MS.
The death of a parent had a nonsignificant 4% increased risk (95% CI 0.90-1.21) of a later MS diagnosis, while death of a sibling before age 18 had a similar nonsignificant 4% impact (95% CI 0.81-1.32).
"There have been conflicting studies over whether stressful events in a person's childhood leads to MS, but in our analysis, we did not find strong evidence for this," Nielsen said during her poster presentation.
"We cannot exclude a biological effect of stress on the susceptibility to MS, but do consider adoption of unhealthy behaviors more likely to explain our findings," she added.
That may be particularly true in the findings on parental divorce. Nielsen said that children's lives may be impacted by living with one parent with reduced income, resulting in less access to healthier lifestyles. Unhealthy lifestyles have been linked to a higher MS risk.
She added that her group will continue to research which life events may confer a risk for MS and disease development.
Nielsen reported no conflicts of interest. A co-author reported relationships with Biogen Idec, Novartis, and Teva.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Nielsen N, et al. "Stressful life-events in childhood and risk of multiple sclerosis" ECTRIMS 2013; Abstract P302.
Source: MedPage Today © 2013 MedPage Today, LLC (07/10/13)
Biomarkers predict second MS attack(07/10/13)
In patients who experienced a first attack of multiple sclerosis (MS) symptoms, risk of a second attack was associated with a variety of baseline factors, researchers said here.
Measurements of brain lesions with MRI, oligoclonal bands in cerebrospinal fluid (CSF), and visual and sensorimotor evoked potentials were, collectively, indicators for patients at relatively high risk of a second attack within 12 months, reported Vittorio Martinelli, MD, of San Raffaele Hospital in Milan.
And, in a separate pan-European study, levels of the chitinase 3-like 1 (CHI3L1) CSF protein were a moderately strong predictor of second attacks in a similar patient population, said Ester Cantó, a PhD student a Vall d'Hebron University in Barcelona.
Using a cutoff value of 190 ng/mL, patients with higher CHI3L1 values showed a median time to develop clinically definite MS by 2005 McDonald criteria of 12.4 months (95% CI 11.8-13.0), compared with 39.5 months in patients with lower CHI3L1 values (95% CI 29.5-50.4), she said.
Both studies were reported at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting, where attention has been particularly focused on the earliest stages of MS.
To qualify for a diagnosis, patients must have experienced two bouts of symptoms separated in time. A first attack is called clinically isolated syndrome (CIS).
In some patients, years may pass until they experience a second attack and are diagnosed with MS -- or never. Others may experience renewed symptoms in as little as 6 months.
Physicians now want to initiate disease-modifying therapies right away in patients with such aggressive pathology, but currently there are no standards for identifying them.
Martinelli noted that previous studies, using different criteria to stratify patients, have found very different rates of conversion from CIS to MS.
Those studies had established some risk factors for conversion: young age, presence of oligoclonal bands in CSF, past steroid treatment, and large MRI lesion burdens.
But narrowing them to establish a reliable predictive model would be useful, he suggested.
Improved Prediction with Conventional Tests
In a step toward that goal, he and colleagues at San Raffaele examined data collected prospectively from 227 CIS patients seen from 2000 through 2010. The data represented results of standard tests for patients with suspected CIS including MRI scans, CSF analysis for oligoclonal bands, and multimodal (visual and sensorimotor) evoked potential testing.
Mean follow-up was 6.8 years (standard deviation 2.8). Mean time from symptom onset to hospitalization and CIS diagnosis was 1.7 months (SD 1.4).
MRI findings at baseline indicated three-quarters of patients had monofocal lesions, with the remainder showing a multifocal distribution. Total T2 lesion counts were zero or one in 12% of patients, from two to nine in 59%, and 10 or more in 29%. Half the patients had gadolinium-enhancing lesions and 74% had oligoclonal bands in CSF.
Just over 30% converted to clinically definite MS within 2 years; through the entire follow-up, 53% converted.
Statistical analysis showed that three factors were most strongly associated with early conversion to MS:
Having more than two T2 lesions
A positive test for oligoclonal bands in CSF
Being in the top quartile of multimodal evoked potentials (indicating impaired peripheral nerve function)
Among patients lacking these three factors, some 15% converted to MS within 12 months, whereas 40% of those showing all three converted.
"Integration of MRI, CSF, and multimodal evoked potential data is essential for an accurate and personalized risk management in patients with CIS," Martinelli said.
CSF Protein Marker
The study reported by Cantó involved CSF samples and clinical data from 813 CIS patients and 559 controls recruited from 15 centers across Europe. Controls included 121 patients with inflammatory neurological diseases that were not CIS or MS.
Her team focused on CHI3L1 due to its appearance in an earlier proteomics discovery project aimed at finding CSF biomarkers that could distinguish early converters from CIS to MS. The current study was designed to validate those findings in a larger, well controlled sample from multiple centers.
In addition, Cantó said, the researchers wanted to understand more about the origins of CHI3L1 within the nervous system.
CIS patients in the study had provided CSF samples during their diagnostic workups. With mean follow-up of 5.4 years, a total of 60% eventually received an MS diagnosis according to 2005 McDonald criteria and 51.5% by the more restrictive Poser criteria.
Across the entire cohort of CIS patients (irrespective of conversion), mean CHI3L1 levels were higher than those in non-inflammatory neurological disease controls by 70 ng/mL, but lower than those in the controls with inflammatory neurological disease by 329 ng/mL (both P<0.0001).
Levels were higher by 40 ng/mL (95% CI 25-56) in patients who converted to MS during follow-up than in those who didn't (P<0.00001), Cantó said.
CHI3L1 levels remained an independent risk factor (P<0.00001) for early conversion when analyzed in a model that also included age at CIS onset, presence of oligoclonal bands, and so-called Barkhof criteria based on MRI findings.
In addition to predicting early conversion to MS, CHI3L1 levels above 190 ng/mL also predicted more rapid disability progression, Cantó said.
Mean time to expanded disability status scale (EDSS) scores of 3.0 was 156 months in those with high values compared with 215 months in those with low values (P=1×10-9).
A histopathology study, using cells from CSF obtained from five CIS patients and five controls with non-inflammatory neurological disease, showed that CHI3L1 expression was localized in MS-type lesions and reactive astrocytes and other activated immune cells.
Cantó said these latter results suggested that elevations in the marker "reflect the degree of astrocyte activation secondary to inflammation."
Both studies had no commercial funding. Quidel provided assays for CHI3L1 but otherwise played no role in the study by Cantó and colleagues.
Martinelli reported relationships with Biogen Dompe, Merck Serono, Bayer Schering, Teva, and Sanofi. Other investigators in his study had relationships with these firms and Genmab.
Cantó reported no conflicts of interest. Other investigators in her study reported relationships with Bayer Schering, Merck Serono, Biogen Idec, Teva, Sanofi, Novartis, Roche, Elan, Genmab, UCB, Wyeth, and others.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Martinelli V, et al. "Predicting early conversion to multiple sclerosis in patients with clinically isolated syndromes: the importance of an integrated modeling of risk factors" ECTRIMS 2013; Abstract 155.
Additional source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference:Canto E, et al. "Validation of cerebrospinal fluid chitinase 3-like 1 as a prognostic biomarker of conversion to multiple sclerosis and disease severity in patients with clinically isolated syndromes" ECTRIMS 2013; Abstract 156.
Source: MedPage Today © 2013 MedPage Today, LLC (07/10/13)
Long-term treatment with serial onabotulinum toxin A (Botox) of urinary incontinence among multiple sclerosis (MS) patients appeared to be safe and effective, researchers reported here.
Daily urinary incontinence episodes due to neurogenic detrusor overactivity dropped dramatically with the 200-unit dose of onabotulinum toxin A from 4.8 episodes a day to an average of about one a day, said Jalesh Panicker, MBBS, MD, from the National Hospital for Neurology and Neurosurgery in London, and colleagues.
That reduction was consistent up to five cycles of treatment, he added during a presentation at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting.
Panicker said that while a higher dose (300 units) of onabotulinum A showed virtually the same results, the 200-unit dose had a better adverse event profile and is approved as the clinical dose.
He said that the higher onabotulinum toxin A showed no additional clinically meaningful benefits, and was associated with more urinary retention and uncomplicated urinary tract infections.
"This is the first, large, multicenter, prospective long-term trial to demonstrate consistent efficacy and tolerability of repeat onabotulinum toxin A treatment in MS patients," the group wrote.
The current research was based on a 3-year, open-label extension study of a phase III trial of onabotulinum toxin A treatment in MS patients with urinary incontinence due to neurogenic detrusor overactivity. The treatment involved up to 30 injections of onabotulinum toxin A into the wall of the bladder, with special attention to avoiding the trigone, he said.
The research team assigned 119 patients to treatment with 200 units of onabotulinum toxin A and 111 patients to the 300-unit dose.
The average age of the study population was 50 and women made up more than three-fourths of patients. They had been diagnosed with neurogenic detrusor overactivity and about half of the participants had previously been treated with anticholinergic drugs. At baseline, 45 of the patients in the 200-unit dose group were using catheters as were 32 in the higher dose group.
Also at baseline, there was an average of 4.8 urinary incontinence episodes per day in the 200-unit group and 4.6 in the 300-unit group.
At week 6, mean reduction in episodes per day ranged from about 3.6 to 4.3 for the 200-unit group and about 3.8 to 4.7 per day for the 300-unit group across treatment cycles one to five, resulting in an average of only one episode per day (range 0.3-1.1), the group reported.
Annualized MS exacerbation rates ranged from 0.06-0.22 across both dose groups for all cycles.
The most common major adverse event following treatment was urinary retention. Panicker said that 29.6% of the patients who had not required catheterization prior to treatment with the 200-unit dose initiated catheter use after the first cycle of treatment. If patients tolerated treatment in the first cycle, the catheterization requirement was greatly reduced in the second (4.3% of patients) and third cycles (6.1%).
The need for initial catheterization due to urinary retention was greater in the 300-unit group, with 44.9% requiring initial catheterization to relieve fluid retention. That dropped to 17.1% after the second treatment cycle and to 4.8 % after the third cycle.
The need for catheterization in both groups was "worrisome," said Vesna Brinar, MD, PhD, from University of Zagreb in Croatia.
"I would be very careful in offering this treatment to my patients," Brinar told MedPage Today. "I am concerned about the high rate of urinary retention that was seen in both doses of onabotulinum A treatment."
"[Catheterization] is very uncomfortable and inconvenient for patients," added Brinar, who moderated the ECTRIMS session where the results were presented. "I think this treatment might be offered to a very carefully selected patient population."
Panicker said about 64% of the original cohort were still on treatment at the time of his presentation. While 79 patients dropped out of the study, just 10 of them quit because of adverse events or lack of efficacy. "During the extension phase of this study, no new safety signals were observed with repeat onabotulinum toxin A treatment," he added.
The trial was sponsored by Allergan.
Panicker disclosed commercial relationships with Allergan, Astellas, AstraTech, and FirstKind. Co-authors also disclosed commercial relationships AMS, Astellas, Hollister, Medtronic, Watson, Coloplast, Contura, NovaBay, Wellspect and Sigma Tau. Other co-authors are employees of Allergan.
Brinar reported no conflicts of interest.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Panicker J, et al "Consistent long-term efficacy of onabotulinumtoxinA in patients with neurogenic detrusor overactivity due to multiple sclerosis: an interim analysis after five treatment cycles" ECTRIMS 2013; Abstract 168.
Source: MedPage Today © 2013 MedPage Today, LLC (07/10/13)
Multiple sclerosis is a debilitating condition that involves the degeneration of myelin—the fatty tissue that insulates nerve fibers and helps them to conduct impulses. This process, called demyelination, can lead to deficits in sensation, movement and thought processes, depending on exactly which nerve fibers are affected. Replacing lost myelin is a promising approach for treating multiple sclerosis and related diseases, but the mechanisms underlying demyelination and remyelination remain poorly understood.
In research that opens up an encouraging avenue for the development of new treatments, Naoyuki Taniguchi and colleagues from the RIKEN–Max Planck Joint Research Center for Systems Chemical Biology have shown that remyelination is inhibited by sugar molecules called branched O-mannosyl glycans.
Taniguchi and his colleagues genetically engineered a strain of mice carrying mutations in the gene encoding an enzyme called N-acetylglucosaminyltransferase-IX (GnT-IX), which catalyzes the branching of O-mannosyl glycan sugars on proteins in the brain. Using these mice, the researchers found that GnT-IX acts on a specific brain protein called receptor protein tyrosine phosphatase ? (RPTP?), which has previously been shown to play a critical role in demyelination.
Next, the research team fed normal and mutant mice a diet containing the neurotoxin cuprizone, which normally induces demyelination. Over the course of eight weeks, the normal mice were found to have experienced gradual demyelination of the corpus callosum—a major tract of white matter connecting the two hemispheres of the brain. By contrast, although myelin in the corpus callosum had degraded by four weeks in the mutants, myelination had markedly increased by the eight-week mark, suggesting that the defect in the GnT-IX gene enhanced remyelination.
Further experiments revealed that cuprizone treatment can activate non-neuronal cells called astrocytes into a disease state, which leads them to express RPTP? containing branched O-mannosyl glycans. In wild-type mice, activated astrocytes express these branched O-mannosyl glycan molecules, which inhibit remyelination. In mice with a defective GnT-IX gene, however, astrocytes are rarely activated, and the absence of the branched O-mannosyl glycans allows the differentiation of myelin cells and the remyelination of nerve fibers in the corpus callosum.
"We would like to unveil the molecular mechanism by which branched O-mannosyl glycan activates astrocytes," says Taniguchi. "Understanding the underlying mechanism is important for developing a drug to treat multiple sclerosis."
The team next plans to screen for a GnT-IX inhibitor that attenuates astrocyte activation. "The difficult thing is that the drug has to pass through the blood–brain barrier, so collaboration with clinicians will be important," Taniguchi notes.
Primary Source: Kanekiyo, K., et al. Loss of branched O-mannosyl glycans in astrocytes accelerates remyelination, The Journal of Neuroscience 33, 10037–10047 (2013). dx.doi.org/10.1523/JNEUROSCI.3137-12.2013
Source: MedicalXpress © Medical Xpress 2011-2013 (04/10/13)
ECTRIMS - NDC-1308 potently enhances remyelination in experimental models of multiple sclerosis(04/10/13)
Scientists from ENDECE Neural presented preclinical data today showing that the company’s lead compound, NDC-1308, addresses one of the root causes of multiple sclerosis (MS) by significantly inducing remyelination in nerves that have been damaged by MS. In an oral presentation at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark, the ENDECE Neural researchers also reported a dramatic upregulation of genes in signaling pathways involved in myelin sheath production.
NDC-1308 works by inducing differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes, cells that synthesize and maintain the myelin sheath that covers nerves in the brain and spinal cord, the researchers noted. By contrast, the female hormones estradiol and estriol do not exert that effect.
“Repair of the myelin sheath, called remyelination, has long been an elusive goal in the treatment of multiple sclerosis,” explained Steven Nye, Ph.D., Vice President of Discovery at ENDECE Neural. “The synthesis of NDC-1308, an estradiol analog, was inspired by observations that pregnant women typically do not experience the symptoms of MS during the third trimester. In our experiments, NDC-1308 induces remyelination in animal models of demyelination, compared to estradiol and estriol which appear to be neuroprotective but do not induce OPC differentiation.”
In his presentation, Dr. Nye described how he and his colleagues synthesized more than 40 proprietary estradiol analogs in which the core structure of estradiol had been modified, and assessed how subsets of those modifications changed the hormone’s biological activity. The researchers identified NDC-1308 as the most potent of several proprietary analogs having the ability to directly induce differentiation of OPCs into mature oligodendrocytes. NDC-1308 derives its novel biological activity from the addition of a specific alkoxyalklyl moiety to the C-6 position on the estradiol B-ring.
Dr. Nye reported the following findings:
- A 20% increase in remyelination (compared to vehicle control) of hippocampal regions of the brain (P<0.01) was associated with a 2-week course of NDC-1308 (50 mg/Kg once daily) in a mouse model of demyelination, in which the neurotoxicant cuprizone was used to remove the myelin sheath from the axons (nerve fibers) of mice.
- NDC-1308 caused a dramatic upregulation of key genes (5- to 75-fold) in signaling pathways involved in OPC differentiation and myelin sheath production.
- NDC-1308 significantly induced OPCs to differentiate into mature oligodendrocytes (P<0.05).
- NDC-1308 (3 μM/day for 4 days) enhanced remyelination in demyelinated rat brain slices visualized by staining for myelin basic protein, which was consistent with the mouse cuprizone data.
Prophylactic administration of NDC-1308 (10 mg/kg/day for 10 days) delayed the onset of MS symptoms and reduced the severity of MS in a mouse model of experimental allergic encephalitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG), suggesting that the compound may play a dual remyelination/anti-inflammatory role in treating MS. “Despite its structural similarity to estradiol and estriol, NDC-1308 differs from those two female hormones by virtue of its potent induction of remyelination, as demonstrated in animal models of MS,” commented James G. Yarger, Ph.D., chief executive officer and co-founder of ENDECE Neural. “Unlike estradiol and estriol, NDC-1308 induces OPC differentiation and maturation of oligodendrocytes. We envision administration of NDC-1308 either alone or in combination with current therapeutics that target the immune response and/or inflammation associated with MS. NDC-1308 may thus fill an unmet medical need for a remyelinating therapy in MS, one that may help improve the lives of patients living with this devastating neurological disease.”
NDC-1308 is a novel chemical entity designed to address one of the root causes of MS, and is being developed for potential use either alone or in combination with other MS therapeutics that slow the progression of the disease. By controlling key genes in pathways leading to myelin synthesis, NDC-1308 appears to induce restoration of the lost myelin sheath that is believed to cause the devastating symptoms of MS. NDC-1308 is a small molecule that readily crosses the blood-brain barrier, allowing it to reach the tissues in the brain and spinal cord where promoting myelin production is needed. ENDECE Neural discovered NDC-1308, and owns the intellectual property surrounding the compound.
Source: Rock Hill Herald Online © Rock Hill Herald Online (04/10/13)
Retinal damage and visual impairment appear to impact African Americans diagnosed with multiple sclerosis more than Caucasian Americans, researchers reported here.
In black MS patients who have a history of optical neuritis there was a significant loss of 4.9 letters -- nearly a line of visual acuity -- when compared with white patients [95% CI minus 8.8-minus 1.0; (P=0.016)], reported Dorian Kimbrough, MD, a post-doctoral fellow in neuroimmunology at Johns Hopkins University.
"Vision represents yet another domain of multiple sclerosis manifestations in which disease activity seems more ominous for African Americans," Kimbrough told MedPage Today at his oral Young Investigator's presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
"There are several domains in multiple sclerosis that appear to be worse in African Americans," he said. "To my knowledge, this is the first study that quantitatively shows that vision and retinal structures are another domain that is worse in African Americans. We don't know the reasons for that yet. We don't know if it has to do with genetic factors or environmental factors."
The research team enrolled 830 individuals into the study, including 137 healthy controls and 693 patients diagnosed with MS at three sites, Johns Hopkins, the University of Pennsylvania in Philadelphia, and the University of Texas Southwestern in Dallas. Patients were recruited and observed from September 2008 through December 2012 and underwent serial optical coherence tomography scans and visual acuity testing during a 4-year period.
Patients self-identified as either African American or Caucasian American, and had relapsing remitting multiple sclerosis or secondary progressive multiple sclerosis. The study excluded individuals with diabetes, glaucoma, uncontrolled hypertension, major refractive errors, or other known eye disorders, Kimbrough said.
The control patients included 106 Caucasian Americans and 31 African Americans. The baseline age for the Caucasians was 32.5; the baseline age for the African Americans was 21.4 years. About 60% of the total cohort was women. The Caucasian controls were followed for about 2 years; the African Americans for 1.3 years.
"There were no clinically significant differences in visual acuity of healthy controls by race at any contrast level," Kimbrough observed. They were tested at contrast levels of 100%, 2.5% and 1%. The results were adjusted for age and sex.
About 88% of the MS patients were Caucasians; more than 75% were women; more than 90% had the relapsing/remitting form of multiple sclerosis. Median follow-up was 2 years.
In healthy African Americans retinal thickness was measured at 5.06 microns thicker than in healthy Caucasians (P=0.025). But in MS patients, retinal thickness was 1.53 microns thinner in African Americans (P=0.367), a non-significant difference.
The manifestations of MS in African Americans is more severe than in Caucasian Americans, Kimbrough said. "African Americans tend to have higher Expanded Disability Status Scale scores and higher multiple sclerosis severity scores at diagnosis," he said. "Markers of intrathecal immunoglobulin synthesis are seen more frequently and at higher levels than in Caucasians. Greater T1 and T2 lesion volumes are seen on MRI."
"I think [visual and retinal damage] is one of several things that doctors should be on the lookout for in African American patients," he said, including overall disability and difficulty in walking. "With this study we have added vision to the list. I think physicians should have more vigilance with African American patients with multiple sclerosis."
Margaret Burnett, MD, clinical professor of neurology and neuropathology at the University of Southern California in Los Angeles, told MedPage Today that "this information is compelling enough for doctors to look for these visual manifestations in African Americans with multiple sclerosis. They definitely should be looking for these symptoms."
Kimbrough disclosed commercial interests with Medical Logix and Teva. Co-authors disclosed commercial interests with Teva, Novartis, Bayer, Biogen Idec, Roche, Acorda, Mylan, Abbott, Genzyme, Prana, Applied Clinical Intelligence, Vertex, Medimmune, and Prothena.
Burnett had no disclosures.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Kimbrough D, et al"Accelerated retinal damage and vision impairment in African-American multiple sclerosis patients" ECTRIMS 2013; Abstract 60.
Source: MedPage Today © 2013 MedPage Today, LLC (04/10/13)
ECTRIMS - Aubagio(R) significantly reduced risk of new clinical relapse or MRI lesion in MS study(03/10/13)
Genzyme, a Sanofi company , announced positive new data from the TOPIC study of its once-daily, oral Aubagio(R) (teriflunomide). These new data, presented today at the 29th Congress of the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS), include the following:
-- Aubagio 14 mg significantly reduced the risk of a new clinical relapse or MRI lesion over the two-year study period. There was a 35 percent reduction among patients who received Aubagio 14 mg compared to placebo (p=0.0003).
-- As measured by MRI over the two-year study period, there was a 5 percent increase in total lesion volume among patients treated with Aubagio 14 mg compared to a 28 percent increase among patients treated with placebo (p=0.0374). In addition, there was a 59 percent reduction in gadolinium-enhancing T1 lesions among patients treated with Aubagio 14 mg compared to placebo (p=0.0008).
Similar results were observed for the 7 mg dose, though the effects did not achieve statistical significance on some endpoints.
The TOPIC trial was designed to assess whether early initiation of Aubagio in patients who experienced their first neurological symptoms suggestive of MS could prevent or delay a second clinical attack, i.e., conversion to clinically definite multiple sclerosis (CDMS).
As previously announced, patients receiving Aubagio 14 mg and 7 mg in the TOPIC trial were significantly less likely than placebo to develop CDMS, the primary endpoint. Compared to placebo, Aubagio 14 mg reduced the risk of conversion to CDMS by 43 percent.
"The findings presented today are encouraging, as they are in line with the body of evidence supporting the value in treating MS early," said Dr. Aaron E. Miller, Medical Director, The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai Medical Center. "These results demonstrate Aubagio's consistent efficacy and safety across a spectrum of MS patients."
The average duration of Aubagio exposure in TOPIC was approximately 16 months. Adverse events observed in the trial were consistent with previous clinical trials with Aubagio in MS. The most common types of adverse events reported more frequently in the Aubagio arms were ALT (Alanine aminotransferase) elevations, headache, hair thinning, diarrhea, paresthesia and upper respiratory tract infection. There were no deaths reported in either Aubagio group over the course of the study. There was one death due to suicide in the placebo arm. The rate of treatment discontinuation due to adverse events was similar across treatment arms (9.9 percent in placebo arm, compared to 12.1 percent in 7 mg Aubagio arm and 8.3 percent in 14 mg Aubagio arm).
"We are proud to share these results, which underscore Aubagio's potential for treating patients in the earlier stages of MS," said Genzyme President and CEO, David Meeker, M.D. "This study, in addition to the studies that support Aubagio's indication in relapsing remitting MS, reflects our commitment to advancing our understanding of this complex disease."
The trial compared treatment with either 14 mg or 7 mg once-daily, oral Aubagio against placebo. This double-blind, multi-center trial enrolled 618 patients who had experienced a first acute or sub-acute, well-defined neurological event consistent with demyelination, as well as onset of MS symptoms within 90 days of randomization, and MRI scan showing two or more T2 lesions characteristic of MS.
Aubagio is approved in the U.S., EU, Australia, Argentina, Chile, South Korea, and Mexico for the treatment of relapsing forms of MS. Marketing applications for Aubagio are also under review by additional regulatory authorities globally.
Source: MarketWatch © 2013 MarketWatch, Inc (03/10/13)
ECTRIMS - New Tysabri data show earlier treatment & longer-term use result in significant reductions in MS disease activity(03/10/13)
Biogen Idec announced results from several new analyses of Tysabri(R) (natalizumab) data that demonstrate its effectiveness in reducing multiple sclerosis (MS) disease activity. This effect was particularly significant in people with relapsing MS who initiated treatment when they had lower Expanded Disability Status Scale (EDSS) scores as well as in those who have been treated for more than two years. These data will be presented at the 29(th) Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark from 2-5 October.
"These analyses build upon a growing body of evidence that demonstrates greater clinical benefits for people with MS when Tysabri is initiated earlier in the course of the disease, as well as when Tysabri is used for a longer duration in appropriate patients," said Alfred Sandrock, M.D., Ph.D., group senior vice president, Development Sciences and Chief Medical Officer, Biogen Idec.
More Patients Demonstrated No Evidence of Clinical or MRI Disease Activity with Earlier Tysabri Use
AFFIRM was a two-year, randomized, multi-center, placebo-controlled, double-blind study of 942 patients evaluating the effect of Tysabri on the rate of clinical relapses and the progression of disability as measured by at least a one-point worsening in EDSS score sustained for three months.
A post-hoc analysis of AFFIRM was undertaken to determine which baseline characteristics were associated with patients showing no evidence of clinical or MRI disease activity (defined as no relapse, no 12-week sustained EDSS progression, and no gadolinium-enhancing [Gd+] or new/enlarging T2-hyperintense lesions) at two years. A greater proportion of Tysabri patients were found to have no evidence of clinical or MRI disease activity compared to those on placebo in all sub-groups analyzed with the beneficial effect being significantly greater in patients with an EDSS score of <3.0 versus >= 3.0 at baseline.
Fewer and Less-Severe Relapses with Tysabri
An additional sub-analysis of AFFIRM assessed the effectiveness of Tysabri on reducing relapse severity and recovery from relapse compared to placebo. Observations from this sub-analysis showed that patients treated with Tysabri experienced less-severe relapses, as measured by EDSS score changes during the relapse and residual deficits following relapse.
These data will be presented in the poster session titled, "Immunomodulation/Immunosuppression," on Friday, 4 October at 3:45 p.m. -- 5:00 p.m. CET:
-- Effects of natalizumab treatment on freedom from disease activity by baseline characteristics in AFFIRM (poster 519)
-- Natalizumab reduces the disabling amplitude of multiple sclerosis relapses and improves post-relapse residual disability (poster 524)
Clinical Benefit of Tysabri Improves Beyond Two Years of Treatment
An analysis of data from the Tysabri Observational Program (TOP), an ongoing observational, open-label, 10-year prospective study of relapsing-remitting MS (RRMS) patients, assessed patients who have been treated with Tysabri for at least four years. The analysis found that patients with less disability at baseline (EDSS score of <3.0 at baseline) had a significantly greater reduction in 12 month sustained disability progression in months 25-48 compared with months 0-24. Additionally, annualized relapse rates (ARR) in patients treated with Tysabri decreased from 2.03 at baseline to 0.19 during months 0-24 and 0.18 during months 25-48 (p<0.0001).
"Tysabri has advanced the treatment of RRMS patients with its established efficacy," Sandrock added. "This analysis is encouraging because it provides new insight into the use of Tysabri beyond two years and suggests that effects of treatment are even better with longer use in appropriate patients."
These data will be presented in the poster session titled, "Long-Term Treatment Monitoring," on Friday, 4 October at 3:30 p.m. -- 5:00 p.m. CET:
-- Disease activity and disability progression decrease beyond 2 years on natalizumab in relapsing MS patients in the Tysabri(R) (natalizumab) Observational Program (poster 1050)
Source: The Wall Street Journal ©2013 Dow Jones & Company, Inc (03/10/13)
ECTRIMS - Gilenya® shown to reduce MS relapse rates compared to interferons or glatiramer acetate(03/10/13)
Novartis announced today findings from an international multiple sclerosis (MS) registry and a US health claims data base which showed the real-world superiority of Gilenya® (fingolimod) in reducing risks of relapses compared to standard therapies. These data confirm the positive results seen in clinical trials with Gilenya, and were presented at the ongoing 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark.
Relapses can make life unpredictable for patients with MS and they can potentially significantly advance an individual's level of disability. MS patients' clinical outcomes are regularly assessed and switching between disease-modifying therapies (DMTs), to reduce the rate or likelihood of a relapse, is a frequent treatment strategy.
"Controlling relapses and preventing disability are key treatment goals for patients with MS." said David Epstein, Division Head of Novartis Pharmaceuticals. "It is encouraging to see that the benefits of Gilenya, which is the only disease modifying treatment proven in clinical studies to have a superior relapse reduction compared to an active comparator, are now confirmed in the real-world setting."
The 'MSBase study', a global, longitudinal, observational registry for MS involving 60 centers in 26 countries and US administrative claims data from the 'IMS PharMetrics PlusTM Database' were interrogated for information on the impact on MS relapses of switching to either oral Gilenya or to one of the standard injectable therapies - an interferon or glatiramer acetate. Collectively, analysis of patient data from these large, real-world databases (416 patients from MSBase and 933 patients from the IMS PharMetrics PlusTM Database) showed that treatment with Gilenya reduced the annualized relapse rate and risk of relapse by approximately 50% compared to therapy with an interferon or glatiramer acetate treatment. They also showed that even amongst patients with MS who have a history of relapse, switching to Gilenya was associated with significant and clinically meaningful reductions in the number of relapses and the probability of experiencing a relapse compared to switching to an interferon or glatiramer acetate.
Following first approvals in 2010, once daily oral Gilenya is now available in more than 75 countries and more than 71,000 patients have been treated in both the clinical trial and post-marketing settings with over 87,000 patient years of exposure.
Source: MarketWatch Copyright © 2013 MarketWatch, Inc (03/10/13)
New imaging test could diagnose MS(03/10/13)
A brand new biomarker that helps visualize multiple sclerosis could one day do for MS what Amyvid has done for Alzheimer's disease.
Associate professor of radiology, chemistry, and biomedical engineering Yanming Wang and his team at Case Western Reserve University developed the biomarker to fill a void in the market.
Physicians currently lack an imaging technique that detects and quantifies myelin sheath damage in the central nervous system — one of the key symptoms of the disease. Myelin damage disrupts nerve signals, resulting in mobility and cognitive dysfunction.
Though MRI can detect brain lesions associated with MS, the lesions could also indicate other unrelated conditions such as edema or inflammation. Doctors rely primarily on behavioral tests to diagnose people with MS.
Multiple sclerosis is the second most common neurodegenerative disease after Alzheimer's.
Experts estimate that between 250,000 to 350,000 people in the United States suffer from the disease. Unlike Alzheimer's, the disease affects young people as well.
Since PET is particularly suited to highlight intact myelin, over the past 10 years researchers have attempted to develop a PET tracer that can visualize myelin damage. With the biotracer, doctors can measure how much myelin remains intact and how much is damaged — an industry first.
Researchers were interested to note that myelin was particularly good for imaging the myelin sheath in the spinal cord — a notoriously hard organ to image.
The test can be used to monitor the progression of the disease over time. But could the scan also be used for diagnosis? "If you have a cohort of patients [cpmprising] normal, healthy subjects, you can get the average outtake and use that as a guideline," Wang said.
In the future, Wang sees two major applications for the probe.
One is to aid researchers in developing a drug to treat MS. Currently MS is treated with symptom-modifying therapy, but to really cure the disease, researchers need an imaging tool that allows them to develop a drug that repairs myelin.
The tool could also potentially be used to monitor the progression of the disease in high-risk individuals so that doctors can treat them before they develop symptoms. "Early treatment is key to treating the disease efficiently," said Wang.
PET is a widely used imaging technique, but its uses are currently limited due to a lack of probes. "This is another step forward to enhance the potential to use PET in routine clinical settings," said Wang.
Researchers are currently initiating clinical trials to get the ball rolling on making the probe available for wider use.
Source: DOTmed Daily News Copyright ©2001-2013 DOTmed.com, Inc (03/10/13)
Patients with radiological signs of multiple sclerosis, even before showing MS-specific symptoms, already had significant brain atrophy relative to healthy controls, a researcher said here.
Mean normalized total brain volume in 12 patients with "radiologically isolated syndrome" (RIS) -- MS-like brain lesions in patients who have not experienced a clear MS-like clinical attack -- was measured via MRI scans at 1.53 L (SD 0.07), compared with 1.64 L (SD 0.03) in 29 neurologically healthy individuals (P=0.003), reported Juan Ignacio Rojas, MD, of Hospital Italiano in Buenos Aires, Argentina.
Gray matter volume after normalization was also significantly lower in the RIS patients relative to controls, with means of 0.56 L (SD 0.07) versus 0.71 L (SD 0.08) and a P value of 0.003 for the difference, Rojas told attendees at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting.
Both brain volume measures in RIS patients were very similar to those found in a third group of 43 patients with clinically isolated syndrome (CIS), the diagnosis for individuals who have recently experienced a first MS-like attack. Patients must have a second attack or show progressive symptoms to receive a diagnosis of clinically definite MS.
Rojas said that measurements of brain volume "might be a useful tool to identify RIS subjects that might be at risk of developing MS," and who therefore could benefit from early treatment with disease-modifying MS agents.
Further analysis of the 12 RIS patients indicated that 42% were eventually diagnosed with CIS, after a mean of 33 months of follow-up, according to an abstract to be presented later in the ECTRIMS meeting.
Because RIS is defined as lacking clear MS-like symptoms, it is identified only as an incidental finding from MRI scans conducted in patients with nonspecific clinical presentations. Among the 12 patients included in the study, six had undergone scans because of unexplained headache, four because of minor trauma, and two because of anxiety, Rojas explained.
But although the lesions in RIS strongly resemble those seen with CIS and full-blown MS, that does not guarantee that the condition always represents a prodromal form of MS. RIS has only been recognized since 2008 and much remains unknown about its relationship to MS, he said.
Approximately half of all three groups in the study were women. Mean age in the RIS patients was 30 (SD 5.4); it was 34 in both the healthy controls and CIS patients (SD 9 and SD 7, respectively).
The MRI measurements in the study also included normalized white matter volume. The means for this parameter were also lower in the RIS and CIS patients relative to controls, but the differences failed to reach statistical significance. Most of the increased atrophy in the RIS group relative to controls was concentrated in the gray matter, Rojas concluded.
None of the slight differences between the RIS and CIS groups approached statistical significance, he reported.
The study was supported by Genzyme.
Ignacio Rojas reported honoraria from Novartis. Other investigators reported relationships with Novartis, Merck Serono, Biogen Idec, Genzyme, and Bayer.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Rojas J, et al "Brain atrophy in radiologically isolated syndrome (RIS)" ECTRIMS 2013; Abstract 62.
Source: Medpage Today © 2013 MedPage Today, LLC (03/10/13)
Patients who received early and consistent disease modifying treatment at the first signs of multiple sclerosis – often called clinically isolated syndrome (CIS) – appeared to have a slower progression to disability than patients who were treated mainly for additional MS exacerbations, researchers reported here.
Over a 12-month period, patients treated 50% to 80% of the time following the first CIS event reduced their risk of progression -- as measured by the Expanded Disability Status Scale score -- by 45% compared with patients who received disease-modifying treatments less than 50% of the time or not at all (95% CI 0.39-0.79, P=0.001), and patients treated for more than 80% of the time following diagnosis reduced their risk of disability progression by 68% (95% CI 0.22-0.49, P<0.001), said Vilija Jokubaitis. PhD, post-doctoral fellow in neuroimmunology at the University of Melbourne.
"What was very interesting about this finding was that the patients who appeared to be worse after their CIS and MRI evaluation and who were treated early, did better than patients whose treatment was delayed," she said in her oral Young Investigators report at the annual meeting of the European Association for the Treatment and Research In Multiple Sclerosis.
About three-fourths of these patients were classified on the basis of T2 lesion enhancement as having relapsing-remitting multiple sclerosis at first treatment. Jokubaitis suggested that because their initial examinations looked worse, the patients were treated more aggressively, and that appeared to have long-term benefits in preventing progression.
"Study after study has shown that early treatment with disease-modifying drugs benefits patients with CIS," said Margaret Burnett, MD, assistant clinical professor of neurology and pathology at the University of Southern California in Los Angeles.
"It kills me that some places still are not treating CIS," she told MedPage Today. "These findings presented here are corroborating evidence that we should be treating CIS and we should make every effort to provide continuous treatment."
In the study, Jokubaitis and colleagues reviewed data involving 1,989 patients for whom complete records were available. The patients had a combined 6,724 years of follow-up with a median follow-up of 3 years per patient – ranging from 9 months to 9.9 years.
Of those patients, 1,339 were treated with disease-modifying agents, either interferon-based products or glatiramer acetate (Copaxone). The researchers included 307 patients who had sustained disability progression over 12 months.
The goal of the study was to determine predictors of progression, and the investigators found that advancing age was a weak prognosticator of disability progression – a 17% increased risk per decade (P=0.006). They also found that pyramidal system dysfunction was a strong predictor of disability progression – with higher imaging pathology translating to a 46% increased risk of disease progression (P=0.008).
Jokubaitis acknowledged that teasing out how treatment affected outcomes was confounded by the fact that sicker patients at diagnosis were more likely to be treated early and consistently, which helped them avoid disease progression.
She and her colleagues did scrutinize the different disease-modifying agents used in the study, but found all of them were successful in delaying progression and none appeared significantly better than the other, although treatment with glatiramer acetate approached significance compared with interferon-beta 1a intramuscular injection (P=0.052) in an ad-hoc analysis.
"Cumulative disease-modifying treatment duration significantly delays progression of multiple sclerosis," Jokubaitis said.
Co-Author Marie Trojano, MD, professor of neurology at the University of Bari in Italy, and president of ECTRIMS, told MedPage Today that concerns that clinically isolated syndromes might not be true multiple sclerosis should be discarded. "There really should not be a disease called CIS. Imaging scans can tell us these events are early multiple sclerosis."
Jokubaitis disclosed commercial interests with Novartis. Co-authors disclosed commercial interests with Biogen Idec, Bayer-Schering, sanofi, Merck-Serono, Teva, Genzyme, Roche, EMD-Serono, GSK and Biologix.
Trojano disclosed commercial interests with Biogen-Idec, Bayer-Schering, sanofi, Merck-Serono, Teva and Novartis.
Burnett had no disclosures.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis Source reference: Jokubaitis V et al, "Predictors of 12-month confirmed disability progression after onset of clinically isolated syndrome (CIS) suggestive of multiple sclerosis" ECTRIMS 2013; Abstract 59.
Source: Medpage Today © 2013 MedPage Today, LLC (03/10/13)
Dr. Ikuo Tsunoda, Assistant Professor in the Department of Microbiology and Immunology at the Center for Molecular and Tumor Virology of the Louisiana State University Health Sciences Center, and colleagues reported that resveratrol, the polyphenol compound produced by the skin of red grapes and peanuts, worsened neuropathology and inflammation and had no neuroprotective effects in multiple sclerosis (MS) in the Oct. 1, 2013, issue of The American Journal of Pathology.
The researchers advise people that have MS or anticipate the development of MS to avoid resveratrol supplements as well as red grapes, peanuts, and red wine as a precautionary measure until further research defines the action of resveratrol in MS.
The researchers induced MS into test mice in two different forms. The diets of the test mice were compared with normal mice. One group of test mice ate a diet high in resveratrol. The other group of mice with MS ate a diet free of resveratrol.
The test mice that had MS and ate a diet high in resveratrol developed symptoms of MS earlier, had higher levels of inflammation, lost more myelin, and demonstrated slower recovery or no recovery from MS than mice that ate a diet free of resveratrol.
Resveratrol demonstrated no anti-viral effects in mice infected with Theiler's murine encephalomyelitis virus the virus used to induce MS like symptoms in test mice.
Source: examiner.com © 2006-2013 Clarity Digital Group LLC (03/10/13)
Credit Suisse sees Copaxone sales falling from $4 billion annually to $400,000 in 2019 and predicts annual sales of over $1 billion for Laquinimod.
Teva Pharmaceutical Industries Ltd, branded drug Copaxone will be the main loser in the multiple sclerosis treatment shift which is currently underway, according to a report by Credit Suisse entitled "Multiple Sclerosis It's a Revolution."
The report says that Tecfidera, the oral multiple sclerosis treatment launched several months ago by Biogen will be the main winner.
Credit Suisse sees annual sales of Copaxone falling 90% from about $4 billion in 2012 to less than $400,000 in 2019. The main reasons for this are well known and have long been acknowledged by investors- competition from rival branded drugs that are new on the market such as Tecfidera, for which it sees sales of $5.2 billion annually by 2019, and Novartis's Gilenya, for which it predicts sales of $3.2 billion annually by 2019. Copaxone will also face competition from generic entries after its patent expires.
Credit Suisse does expect Laquinimod, Teva's oral treatment for multiple sclerosis, to come onto the market by 2017 but sees annual worldwide sales of only $428 million in the US and $649 million in the rest of the world by 2019.
Source: Globes [online], Israel business news © Copyright of Globes Publisher Itonut (1983) Ltd. 2013 (02/10/13)
GW Pharmaceuticals PLC said new test data had reinforced the efficacy and safety profile of its Sativex drug for treatment of Multiple Sclerosis spasticity.
It said the latest results from several studies show that the drug's effectiveness is maintained long term with no additional safety concerns identified in clinical practice.
It will present the data Wednesday at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Copenhagen.
Sudies in specialist MS centres across the EU showed improvements in spasticity were confirmed by more than 70% of patients, but also by physicians and carers, with Sativex was generally well tolerated, GW Pharma said in a statement.
Another study conducted in three German centres showed the drug had no adverse effects on driving ability, the MS spasticity and spasms count improved and the treatment was again well tolerated.
Sativex is a cannaboid which is administered in spray form. It has been launched in 11 countries including the UK, Spain, Italy and Germany, and has approvals for a further 11 countries.
GW Pharma shares were up 2.4% at 86.78 pence Wednesday morning.
By Steve McGrath; firstname.lastname@example.org; @SteveMcGrath1
Source: Copyright 2013 Alliance News Limited. All Rights Reserved. (02/10/13)
The number of people living with multiple sclerosis around the world has increased by 10 percent in the past five years to 2.3 million, according to the most extensive survey of the disease to date.
The debilitating neurological condition, which affects twice as many women as men, is found in every region of the world, although prevalence rates vary widely.
Multiple sclerosis (MS) is most common in North America and Europe, at 140 and 108 cases per 100,000 respectively, while in sub-Saharan Africa the rate is just 2.1 per 100,000, the Multiple Sclerosis International Federation's Atlas of MS 2013 showed on Wednesday.
The atlas also confirmed that MS occurs significantly more in countries at high latitude, with Sweden having the highest rate in Europe and Argentina having more cases than countries further north in Latin America.
The reason for the link to high latitudes is unclear but some scientists have suggested that exposure to sunlight may reduce the incidence of the disease.
The survey found a big increases in the number of medical experts trained to diagnose MS and help patients with treatment, while the number of magnetic resonance imaging (MRI) machines available to carry out scans has doubled in emerging countries.
But huge disparities remain when it comes to access to modern disease-modifying drugs.
MS medicine has seen a number of advances in recent years, particularly with the introduction of a new generation of oral therapies such as Novartis' Gilenya, Biogen Idec's Tecfidera and Sanofi's Aubagio.
These medicines offer an effective alternative to older disease-modifying treatments that are given by injection.
The survey found that injectable drugs like Biogen's Avonex and Teva's Copaxone were partly or fully funded in 96 percent of high-income countries, while Gilenya was available in 76 percent.
However, none of these drugs was available under government programmes in low-income countries.
Source: Thomson Reuters Copywrite 2013 Thomson Reuters (02/10/13)
When I have diagnosed patients with multiple sclerosis (MS) to be gluten intolerant, the results of implementing a gluten-free diet are often an improvement of their MS and nervous system related symptoms. When they related their improvement to their neurologist, it was frequently met with disbelief or a comment that implied some type of ‘placebo’ effect. Understandably, patients would be very frustrated at the dismissal of what they felt was a significant factor in their health.
While in the past, I’ve only had my clinical experience as a clinical nutritionist to stand on in support of how gluten affects M.S., we now have a wonderful study that reveals the strong correlation between gluten intolerance and MS.
BMC Neurology published a study entitled “Prevalence of Celiac Disease in Multiple Sclerosis” where they reported that the population of individuals suffering from MS appeared to be 5 to 10 times more likely to develop celiac disease than the general population. Interestingly, their first degree relatives were 16 to 32 times more likely to develop celiac disease.
Celiac disease is understood to be associated with different autoimmune and neurological diseases. To see how this potentially related to MS, the researchers examined 72 patients suffering with MS along with their 125 first-degree relatives and compared them to 123 healthy controls.
10% of the MS patients were found to have positive blood tests for celiac disease as compared to 2% of the healthy controls. [Note: this study found 2% of the ‘general population’ to have celiac disease. This is significant for we have used the figure of 1% incidence for quite some time. It is my belief that it IS higher and this study certainly gives merit to that supposition.]
Examining the same individuals through biopsy, 11% of the MS patients had celiac disease. Additionally, an astounding 32% of their first-degree relatives were also found to have celiac disease. No comment was made as to reasons why first-degree relatives would have such a marked increase, but it is quite fascinating.
Could it be that those with neurological illnesses, especially of the autoimmune variety should not only be tested themselves for celiac disease, but should also ensure that their family members be screened?
Conditions known to be associated with celiac disease, including dermatitis and iron deficiency anemia, were found in 57% and 39% of the MS patients respectively. Not surprisingly, considering that MS and celiac disease are both autoimmune diseases and where there is one autoimmune condition there is usually more, the researchers also found indications of other autoimmune conditions present in these affected individuals. Specifically, autoimmune thyroid disease was found in 26% and rheumatoid arthritis in 15% of the MS patients.
When a gluten free diet was instituted, all of the MS patients with celiac disease improved ‘considerably’. Not only did their digestive complaints improve but so did their nervous system symptoms.
Dr. Rodrigo, the main researcher stated that: “So the main message that we want to [get out] to doctors who attend MS patients is to perform clinical, serological [blood], genetic, and histologic [biopsy] studies directed to find a possible associated [celiac disease]“.
Source: Copyright © Health Now Medical. All Rights Reserved. 2013 (02/10/13)
Teva Pharmaceutical Industries Ltd. and Active Biotech have announced the publication of a pre-planned analysis of the Phase III ALLEGRO study demonstrating that once-daily oral laquinimod provides a beneficial impact on brain tissue damage, one of the most destructive aspects of multiple sclerosis. These data, "Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage," published online in September by the Journal of Neurology, Neurosurgery & Psychiatry (JNNP), along with an accompanying editorial titled, "Oral laquinimod for multiple sclerosis: beyond the anti-inflammatory effect," can be found on the JNNP website at www.jnnp.bmj.com.
"This Phase III sub-study was pre-planned to explore the ability of laquinimod to act on mechanisms leading to irreversible brain tissue damage," said Professor Massimo Filippi, Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University. "This study indicates that laquinimod likely exerts a favourable effect on several MRI metrics of neurodegeneration, which in turn might explain the previously observed ability of the drug to significantly slow down progression of locomotor disability in relapsing-remitting multiple sclerosis."
The results showed that when compared with placebo, patients treated with laquinimod experienced decreased rates in brain tissue damage shown by various MRI markers. Specifically, patients receiving laquinimod showed decreased rates of white matter (WM), grey matter (GM) and thalamic atrophy; developed fewer permanent black holes (PBH); and accumulated less damage in normal appearing brain tissue (NABT), WM and GM, when compared to patients receiving placebo.
"These analyses reinforce our faith in the potential of laquinimod and we are proud to announce that we plan to initiate a clinical trial of the drug in PPMS to gather even more evidence of this novel mechanism of action," said Dr. Michael Hayden, President of Global R&D and Chief Scientific Officer for Teva Pharmaceutical Industries Ltd. " We also believe the potential neuroprotective benefits of laquinimod could have significant application in the treatment of other diseases like Crohn's disease, lupus nephritis, Huntington's disease and Alzheimer's."
A third Phase III laquinimod trial, CONCERTO, is evaluating two doses of the investigational product (0.6mg and 1.2mg) in approximately 1,800 patients for up to 24 months. The primary outcome measure is the time to confirmed disability progression as measured by the EDSS. The study will also examine the impact of laquinimod on endpoints such as percent change in brain volume, as well as other clinical and MRI markers of disease activity.
ABOUT THE ALLEGRO STUDY
ALLEGRO was a two-year multi-national, multi-center randomized, double blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of laquinimod in MS patients. The study was conducted at 139 sites in 24 countries and enrolled 1,106 MS patients. Patients were randomized to receive a once-daily oral dose of 0.6 mg laquinimod or matching placebo. The primary outcome measure was the number of confirmed relapses; secondary measures included confirmed disability progression and changes in MRI active lesions.
In the ALLEGRO study, laquinimod showed a statistically significant 23 percent reduction in annualized relapse rate (p=0.0024), the primary endpoint, along with a significant 36 percent reduction in the risk of confirmed disability progression, as measured by Expanded Disability Status Scale (EDSS) (p=0.0122). Treatment with laquinimod was also associated with a significant reduction in brain tissue loss, as measured by a 32.8 percent reduction in progression of brain atrophy (p<0.0001).
In these MRI analyses, white matter (WM), grey matter (GM) and thalamic fractions were derived at baseline, and months 12 and 24. Also assessed were evolution of gadolinium enhancing and/or new T2 lesions into permanent black holes (PBH); magnetization transfer ratio (MTR) of normal-appearing brain tissue (NABT), WM, GM and T2 lesions as assessed by magnetization transfer (MT) MRI; and changes in n-acetylaspartate/creatinine (NAA/Cr) levels.
Eighty percent of laquinimod and 77 percent of placebo patients completed the two-year study. Patients who completed the ALLEGRO study were offered to join an open-label extension phase, in which they are being treated with laquinimod 0.6 mg daily.
The safety and tolerability profile of laqunimod observed in the ALLEGRO and BRAVO studies was favorable. The overall frequencies of adverse events, including incidence of infections, were similar to those observed in the placebo group. The most commonly reported adverse events were headaches, nasopharyngitis and back pain. The incidence of liver enzyme elevation was higher in laquinimod treated patients; however, these elevations were transient, asymptomatic and reversible.
Laquinimod is an oral, investigational, CNS-active immunomodulator with a novel mechanism of action being developed for the treatment of relapsing-remitting MS (RRMS). The global Phase III clinical development program evaluating oral laquinimod in MS includes two pivotal studies, ALLEGRO and BRAVO. A third Phase III laquinimod trial, CONCERTO, is evaluating two doses of the investigational product (0.6mg and 1.2mg) in approximately 1,800 patients for up to 24 months. The primary outcome measure is the time to confirmed disability progression as measured by the EDSS.
In addition to the MS clinical studies, laquinimod is currently in Phase II of development for Crohn's disease and lupus nephritis. Because of the neuroprotective findings, Teva is evaluating further studies to determine the effectiveness of laquinimod in treating patients with primary progressive multiple sclerosis, Huntington's disease and Alzheimer's disease.
Source: The Wall Street Journal ©2013 Dow Jones & Company, Inc (01/10/13)
Biogen Idec announced new data analyses from year one of the two-year, pivotal, Phase 3 ADVANCE study of PLEGRIDY(TM) (peginterferon beta-1a). PLEGRIDY is an investigational subcutaneous injectable for relapsing forms of multiple sclerosis (RMS), in which interferon beta-1a is pegylated to prolong the molecule's exposure in the body and enable the study of a less frequent dosing schedule. Clinical and MRI data from the study demonstrated a reduction in relapses, disability progression and the number of MS lesions when compared to placebo, and further support the clinical efficacy profile of PLEGRIDY. These data will be presented this week at the 29(th) Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark 2-5 October.
"If approved, PLEGRIDY could become a valuable addition to the interferon class of multiple sclerosis therapies," said Professor Peter Calabresi, MD, director, The Johns Hopkins Multiple Sclerosis Center. "The combination of efficacy demonstrated across key disease measures and a less frequent dosing schedule has the potential to offer an important therapeutic option for people living with MS."
Improvements Seen in Clinical and MRI Endpoints
Over one year, absence of measured disease activity (defined as no relapses, no disability progression, no gadolinium-enhancing [Gd+] lesions and no new or newly enlarging T2-hyperintense lesions compared to baseline) among patients, was significantly higher with PLEGRIDY: 34 percent in the two-week dosing arm (p<0.0001) and 22 percent in the four-week dosing arm (p=0.01), compared to 15 percent in the placebo arm.
In the intent-to-treat population of the ADVANCE study, PLEGRIDY, when dosed every two weeks, significantly reduced the number of new or newly enlarging T2-hyperintense lesions, new T1-hypointense lesions, new Gd+ lesions and new active lesions compared to placebo at 48 weeks. Specifically, PLEGRIDY reduced the number of:
-- New T1-hypointense lesions by 53 percent in the two-week dosing arm (p<0.0001) and 18 percent in the four-week dosing arm (p=0.082), ns
-- New active lesions by 67 percent in the two-week dosing arm (p<0.0001) and 35 percent in the four-week dosing arm (p<0.0001)
And, as previously reported at the American Academy of Neurology's 65(th) Annual Meeting in March 2013:
-- New or newly enlarging T2-hyperintense lesions by 67 percent in the two-week dosing arm (p<0.0001) and 28 percent in the four-week dosing arm (p=0.0008)
-- New Gd+ lesions by 86 percent in the two-week dosing (p<0.0001) and 36 percent in the four-week dosing arm (p=0.07), ns
"We believe the new analyses reinforce the efficacy of PLEGRIDY, which has been shown consistently across key MS disease measurements. They further support its potential as a treatment option for people living with this disease," said Gilmore O'Neill, vice president, Global Neurology Clinical Development at Biogen Idec. "The ADVANCE study results we have seen to date indicate that PLEGRIDY may have a positive effect on the reduction of relapses, disability progression and the reduction of lesion development."
Clinical and MRI results, including a post-hoc analysis evaluating the absence of measured disease activity from year one of the ADVANCE study, will be presented in the poster session titled, "Immunomodulation/Immunosuppression," on Thursday, 3 October at 3:45 p.m. -- 5:00 p.m. CET:
-- Peginterferon Beta-1a Provides Improvements in Clinical and Radiological
Disease Activity in Relapsing Multiple Sclerosis: Year 1 Findings from the Phase 3 ADVANCE Study (poster 514)
Additional MRI results from the first year of ADVANCE will be presented in the poster session titled, "II Immunomodulation/Immunosuppression," on Friday, 4 October at 3:30 p.m. -- 5:00 p.m. CET:
-- Magnetic Resonance Imaging Results from the First Year of the ADVANCE Study, a Pivotal Phase 3 Trial of Peginterferon Beta-1a in Patients with Relapsing-Remitting Multiple Sclerosis (poster 989)
PLEGRIDY is a new molecular entity in which interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body. PLEGRIDY is a member of the interferon class of treatments, which is often used as a first-line treatment for MS.
Regulatory authorities in the United States and the European Union accepted the marketing applications for the review of PLEGRIDY in RMS in July 2013.
The two-year Phase 3 ADVANCE clinical trial is a global, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the efficacy and safety of PLEGRIDY in 1,516 patients with relapsing-remitting MS. The study investigates two dose regimens of PLEGRIDY: 125 mcg administered subcutaneously every two weeks or every four weeks compared to placebo. The analysis for all primary and secondary efficacy endpoints occurred at one year.
In the ADVANCE clinical trial, PLEGRIDY met all primary and secondary endpoints by significantly reducing disease activity, including relapses and disability progression, compared to placebo, and showed favorable safety and tolerability profiles at one year. PLEGRIDY also reduced the number of new or newly enlarging T2-hyperintense lesions and the number of Gd+ lesions on brain MRI scans after one year.
After the first year, patients on placebo are re-randomized to one of the PLEGRIDY arms for the duration of the second year of the study. After completing two years in the ADVANCE study, patients have the option of enrolling in an open-label extension study called ATTAIN and will be followed for up to four years.
Source: The Wall Street Journal ©2013 Dow Jones & Company, Inc (01/10/13)
For young people, type 1 diabetes may raise the likelihood of having multiple sclerosis. Scientists now suspect that certain environmental factors may play a role.
Type 1 diabetes and multiple sclerosis (MS) are both autoimmune diseases, meaning a person's immune system causes damage to their own body.
Type 1 diabetes (sometimes called juvenile diabetes because it is usually diagnosed in childhood) is an autoimmune attack against the beta cells in the pancreas while, with multiple sclerosis, the immune system attacks the brain and spinal cord.
Recent research backed up previous studies which found that children and adolescents with diabetes face greater odds of getting MS. Investigators discovered that environmental factors, including when a person is born, may heighten this risk.
Susanne Bechtold, MD, in the Department of Pediatrics, Medical University Munich, Germany, and a team of researchers analyzed data on 56,653 children and adolescents with type 1 diabetes under the age of 21 from Germany and Austria.
The authors discovered 19 of these patients had MS.
Researchers compared MS prevalence rates from the Mid-European and German MS pediatric and adult registers with their data. They calculated an MS prevalence of 7 to 10 patients per 100,000 with type 1 diabetes, compared with 3 to 5 cases per 100,000 in a non-diabetes population.
The risk of the diabetes patients having MS was three to almost five times greater.
The investigators also cited three possible influencing factors that could be adding to the risk of developing MS—immigration status, thyroid antibodies (only in males) and month of birth.
There was a higher MS risk in patients with an immigrant background. The authors wrote "...we assume that variations in their genetic, environmental or cultural background caused this significantly increased risk to simultaneously develop type 1 diabetes and MS."
Male patients with thyroid specific antibodies also had a higher chance of developing MS. Thyroid antibodies are an immune response of the body, which is considered to be abnormal.
Also, researchers noted that among the diabetes-MS patients, dates of birth peaked in June and August.
Dr. Bechtold told dailyRx News, “We think that environmental factors might influence the immunological system, like by vitamin D level during early pregnancy. The theory regarding month of birth is that vitamin D has immune-modulating capacities.”
This study found that two-thirds of patients with type 1 diabetes and MS had a birth month consistent with the fetus having experienced lower levels of ultraviolet exposure during early pregnancy. Exposure to sunlight can be a source of vitamin D.
“Overall this is speculation and I am not aware on any study investigating the influence of different environmental factors in detail on the fetus,” said Dr. Bechtold.
The authors qualified their results, writing that the low number of MS patients did not reach statistical significance.
“In the next step, we are going to contact each of the 19 patients to get more detailed information of history, family history and immunological data,” Dr. Bechtold told dailyRx News. “Only with these hopefully more detailed knowledge we may give advice.”
The study was published online in September in Diabetes Care ahead of print.
Source: dailyRX © 2013 dailyRx, Inc (30/09/13)
Objectives & Methods: We evaluated internal jugular vein and vertebral vein volume flow using ultrasound, in patients with clinically isolated syndrome or mild multiple sclerosis and controls, to determine whether volume flow was different between the two groups.
Results: In patients and controls, internal jugular vein volume flow increased from superior to inferior segments, consistent with recruitment from collateral veins. Internal jugular vein and vertebral vein volume flow were greater on the right in supine and sitting positions. Internal jugular vein volume flow was higher in the supine posture. Vertebral vein volume flow was higher in the sitting posture. Regression analyses of cube root transformed volume flow data, adjusted for supine/sitting, right/left and internal jugular vein/vertebral vein, revealed no significant difference in volume flow in patients compared to controls.
Conclusions: Our findings further refute the concept of venous obstruction as a causal factor in the pathogenesis of multiple sclerosis. Control volume flow data may provide useful normative reference values.
Internal jugular and vertebral vein volume flow in patients with clinically isolated syndrome or mild multiple sclerosis and healthy controls: results from a prospective sonographer-blinded study. - Chambers B, Chambers J, Churilov L, Cameron H, Macdonell R.
Department of Neurology, Austin Health, Melbourne, Australia.
Source: Phlebology. 2013 Sep 24. [Epub ahead of print] & Pubmed PMID: 24065289 (30/09/13)
Many people with MS start using some kind of mobility aid -- cane, walker, scooter or wheelchair -- by 45 or 50, and those with the most severe cases are typically bed-bound by 60. The medications that are currently available don't do much to slow the relentless march of the disease.
In search of a better option for MS patients, a team of University of Wisconsin-Madison biochemists has discovered a promising vitamin D-based treatment that can halt -- and even reverse -- the course of the disease in a mouse model of MS. The treatment involves giving mice that exhibit MS symptoms a single dose of calcitriol, the active hormone form of vitamin D, followed by ongoing vitamin D supplements through the diet. The protocol is described in a scientific article that was published online in August in the Journal of Neuroimmunology.
"All of the animals just got better and better, and the longer we watched them, the more neurological function they regained," says biochemistry professor Colleen Hayes, who led the study.
MS afflicts around 2.5 Million people worldwide, with 200 new cases diagnosed each week. Early on, this debilitating autoimmune disease, in which the immune system attacks the myelin coating that protects the brain's nerve cells, causes symptoms including weakness, loss of dexterity and balance, disturbances to vision, and difficulty thinking and remembering. As it progresses, people can lose the ability to walk, sit, see, eat, speak and think clearly.
Current FDA-approved treatments only work for some MS patients and, even among them, the benefits are modest. "And in the long term they don't halt the disease process that relentlessly eats away at the neurons," Hayes adds. "So there's an unmet need for better treatments."
While scientists don't fully understand what triggers MS, some studies have linked low levels of vitamin D with a higher risk of developing the disease. Hayes has been studying this "vitamin D hypothesis" for the past 25 years with the long-term goal of uncovering novel preventive measures and treatments. Over the years, she and her researchers have revealed some of the molecular mechanisms involved in vitamin D's protective actions, and also explained how vitamin D interactions with estrogen may influence MS disease risk and progression in women.
In the current study, which was funded by the National Multiple Sclerosis Society, Hayes' team compared various vitamin D-based treatments to standard MS drugs. In each case, vitamin D-based treatments won out. Mice that received them showed fewer physical symptoms and cellular signs of disease.
First, Hayes' team compared the effectiveness of a single dose of calcitriol to that of a comparable dose of a glucocorticoid, a drug now administered to MS patients who experience a bad neurological episode. Calcitriol came out ahead, inducing a nine-day remission in 92 percent of mice on average, versus a six-day remission in 58 percent for mice that received glucocorticoid.
"So, at least in the animal model, calcitriol is more effective than what's being used in the clinic right now," says Hayes.
Next, Hayes' team tried a weekly dose of calcitriol. They found that a weekly dose reversed the disease and sustained remission indefinitely.
But calcitriol can carry some strong side effects -- it's a "biological sledgehammer" that can raise blood calcium levels in people, Hayes says -- so she tried a third regimen: a single dose of calcitriol, followed by ongoing vitamin D supplements in the diet. This one-two punch "was a runaway success," she says. "One hundred percent of mice responded."
Hayes believes that the calcitriol may cause the autoimmune cells attacking the nerve cells' myelin coating to die, while the vitamin D prevents new autoimmune cells from taking their place.
While she is excited about the prospect of her research helping MS patients someday, Hayes is quick to point out that it's based on a mouse model of disease, not the real thing. Also, while rodents are genetically homogeneous, people are genetically diverse.
"So it's not certain we'll be able to translate (this discovery to humans)," says Hayes. "But I think the chances are good because we have such a broad foundation of data showing protective effects of vitamin D in humans."
The next step is human clinical trials, a step that must be taken by a medical doctor, a neurologist. If the treatment works in people, patients with early symptoms of MS may never need to receive an official diagnosis.
"It's my hope that one day doctors will be able to say, 'We're going to give you an oral calcitriol dose and ramp up the vitamin D in your diet, and then we're going to follow you closely over the next few months. You're just going to have this one neurological episode and that will be the end of it,'" says Hayes. "That's my dream."
Source: ScienceDaily Copyright 2013 by ScienceDaily, LLC (30/09/13)
A major milestone has been reached on the path to finding a cure for multiple sclerosis (MS), researchers say.
A group of international scientists, including an Australian contingent, has discovered 48 previously unknown genes that influence the risk of developing MS.
MS, which attacks a person’s central nervous system and can impact mobility, balance and sensation, affects 23,000 Australians.
The new discovery is a big step towards finding a cure and further treatment for the debilitating condition, says University of Sydney Associate Professor David Booth, who led the Australian and New Zealand component of the study.
“The exciting thing about this is we have doubled the number of genes that we now know are associated with MS,” he’s told Sydney media.
“What that means is every one of those new genes is potentially providing us with a new way to understand the disease and to come up with new therapies for the disease.”
Researchers say they believe the findings underline the central role the immune system plays in the development of MS.
The results also show an overlap with genes found to be linked to other auto-immune diseases, including inflammatory bowel disease and coeliac disease.
The team of scientists, working under the umbrella of the International Multiple Sclerosis Genetics Consortium, has its findings published in medical journal Nature Genetics today (Monday, September 30).
As part of the study, the largest investigation of MS genetics to date, DNA from blood samples from 80,000 people with and without the condition were examined, including 1800 from Australia and New Zealand.
Professor Booth says the “milestone” provided specific research targets.
“So going forward we will try and find out why all of these genes affect MS,” he says.
“And particularly finding which processes are tagged by groups of genes and that will give us specific information on immune processes that are not functioning as they should.”
As a result of the new findings, there are now 110 genetic variants linked to MS.
MS Research Australia’s CEO Matthew Miles says the work is a huge contribution to understanding MS.
Source: Cowra Community News © 2013 Cowra Community News (30/09/13)
A new study published today suggests that significantly more people are living with MS than previously thought. National charity MS-UK questions whether adequate provisions are available.
The study estimates that the number of people living with MS is now 127,000, some 27% more than previously thought.
Abi Crawford, interim CEO of MS-UK said “The outcome of this study is sobering. For far too long the services available to people affected by MS have been woefully inadequate.
MS-UK’s ethos has always been that taking a practical yet encompassing approach to managing MS can help improve well-being both physically and mentally.
As a charity, MS-UK has seen an increase in demand for our services which demonstrates the essential need for them to be available.”
Between 1990 – 2010, the study showed the number of people living with MS increased by 2.4% each year partly due to falling mortality rates, showing that people with MS are living longer.
Ms Crawford went on to say “People with MS are now living longer with the incurable and unpredictable condition. It is essential that people not only learn to live with their condition but also that they can have a fulfilling life. We hope that the study prompts a heightened awareness of MS and the impact it can have on people’s lives. More importantly, we hope that more resources are made available.”
MS-UK provides support, information and advice to anyone affected by MS and can be contacted on 0800 783 0518 or by visiting www.ms-uk.org .
MS-UK Press Release (27/09/13)