MS news and research
This page documents breaking multiple sclerosis news and research stories as they occur during the month.
For news and research for the previous 12 months please use the links on the menu on the left.
The news stories are taken from external sources and as such, MS-UK does not verify, endorse or accept responsibility for their content.
Some of these pages have been written for medical professionals and this can be reflected in the complexity of language and content. If you have any issues relating to the topics here, please call the MS-UK Helpline on 0800 7830 518.
Patients want full disclosure(06/03/15)
Individuals with multiple sclerosis want to know what’s going on behind closed doors concerning drug research, according to a study published in the Multiple Sclerosis Journal. The study shows MS patients want full disclosure concerning the financial relationship between the doctors and the drug companies in pharmaceutical industry-sponsored clinical trials (ISCTs) before they will agree to participate in such research.
Andrew Solomon, MD, a neurologist and MS specialist at the University of Vermont, and his colleagues from several other universities and medical centers, came to this conclusion after reviewing the responses on an anonymous survey completed by 522 individuals with multiple sclerosis.
Participation in clinical trials has the potential to provide benefits for the subjects as well as other current and future patients, along with yielding critical information for the investigators. However, when there are financial relationships between physicians and pharmaceutical companies involved in such research, red flags are raised about bias and the validity of the findings.
When agreeing to participate in pharmaceutical industry-sponsored clinical trials (as well as other types of clinical trials), patients are provided with information about the study, including its risks, in an informed consent document, which needs to be signed before participating in the research. Currently, however, patients do not see information concerning potential financial conflicts of interest regarding the participating physicians, such as monies generated by the trial or fees given to the doctors for consulting services or speaking engagements.
According to Solomon, he and his associates decided to conduct this study because “direct industry financial support of physicians, physician practices, and academic departments involved in MS therapy-related multicenter ISCTs are an infrequently acknowledged source of potential physician conflict of interest,” and they wanted to know how individuals with multiple sclerosis felt about this topic.
The authors learned that most of the surveyed individuals with multiple sclerosis believed that it was important for doctor-pharmaceutical company relationships to be disclosed. Respondents also rated monies paid toward the principal investigator’s salary as the most important thing they wanted to know about the physician-drug industry financial relationships.
Solomon and his team, who noted that “avoidance or minimization of potential conflicts of interest is the goal,” also stated that more research is needed on this issue.
Source: EmaxHealth 2015 (06/03/15)
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A new survey, conducted by Pain UK and St. Jude Medical, has found that although 66 per cent of people see their GP for chronic pain, the majority do not see a specialist or visit a pain clinic.
Almost ten million people in the UK suffer from chronic pain, according to Pain UK, which has a major impact on quality of life and day to day activities, such as work.
However many of those people do not have their pain under control or know how to go about seeking the right treatment. The new survey interviewed 1,614 people (1,090 general respondents and 524 chronic pain sufferers), and found that although chronic pain is quite prevalent, there is a general lack of awareness about what chronic pain is and how it should be treated.
Chronic pain is defined as continuous, long-term pain lasting more than 12 weeks or pain that remains after discomfort would traditionally recede after trauma or surgery. However, recent survey results revealed only 30 per cent of people surveyed who do not suffer from chronic pain actually understand what chronic pain is and how long it lasts. Additionally, for those who do suffer from chronic pain, results indicate many do not seek treatment any further than visiting their GP. In fact, only 15 per cent of those surveyed who suffer from chronic pain have actually visited a pain clinic to receive proper treatment and there is a general lack of awareness about treatments other than ‘painkiller’ medication.
Antony Chuter, of Pain UK, said: “The results of this survey show there needs to be increased awareness throughout the UK about chronic pain and how it should be treated. As this survey demonstrates, many people who are in chronic pain in the UK seek treatment, but go no farther than their GP. Patients should be educated about the treatment options available and also when to see a specialist and GPs should refer patients to pain clinics when necessary.”
Dr Vivek Mehta, consultant pain physician, Barts Health NHS Trust, said: “The statistics uncovered in this survey are concerning and a definite indication that awareness must be increased about chronic pain and the proper treatment for it. Although people believe that chronic pain is an actual condition, many are unaware of the treatment options and are living with a condition that has a profound negative impact on their quality of life. Aside from medication, there are numerous types of treatment available for people living with chronic pain, particularly failed back surgery, such as spinal cord stimulation, which works by implanting a “pacemaker” or a form of pulse generator that stimulates the nerves electronically in order to control the pain, and research is showing it to be an effective treatment in reducing patient’s pain. However, people across the UK are not accessing these types of treatment.”
Source: Pain UK (05/03/15)
Businesses missing out on £1.8bn a month(05/03/15)
A report released today by the Extra Costs Commission led by disability charity Scope has found that 75 per cent of disabled people and their families have walked away from a UK business due to poor service.
Drawing upon research conducted by Business Disability Forum (BDF) in 2006 on the income lost by businesses that fail to make goods and services accessible to disabled people, the Commission surveyed over 2,000 disabled people to find businesses are losing an estimated £1.8bn a month by ignoring the needs of disabled customers.
Three out of four people reported they and families moved spending away from businesses including supermarkets, banks, utilities, restaurants and transport companies as a result of poor service and lack of disability awareness.
A UK business membership organisation working with large private and public businesses that account for nearly 20 per cent of the UK workforce, BDF welcomed the report, which they say adds to a growing business case for improving accessibility and usability of products and services for disabled people.
George Selvanera, Director of Policy, Services & Communications at BDF, said: “The findings of the Commission's report are a call to action for business to seek out new ways of improving the customer experience for disabled people. The rapid ageing of the UK population, growing numbers of older and disabled people and changing technology make the case for business investing in improving accessibility more and more compelling.
“At BDF, we know it is not all bad news. Companies such as Barclays Bank, Enterprise Rent-A-Car, Sainsbury’s, BT and others are leading the way in inclusive design and improving the disabled and older customer experience. There is more to do definitely, but there is learning from some of the best.”
Warren Buckley, Chair of BDF, said: “The opportunities are there for businesses to grasp. We work with those that are already supplying excellent customer service, and this reports sets out how they can get even better at supplying of goods and services to disabled people.
“The Government value the purple pound at over £200bn. Businesses that improve how they work with disabled consumers will have an advantage over their competitors.”
Source: Business Disability Forum (05/03/15)
Genetic risk factor uncovered(05/03/15)
Researchers at the University of Illinois at Chicago have identified a genetic variation that in women significantly increases their risk of developing multiple sclerosis. The report is published in the journal ASN Neuro.
The variant occurs almost twice as often among women with MS as in women without the disease, making it "one of the strongest genetic risk factors for MS discovered to date," said senior author Doug Feinstein, professor of anesthesiology at UIC and research biologist at the Jesse Brown VA Medical Center.
Feinstein and his colleagues were able to test three sisters among a group of five siblings between the ages of 23 and 26, all diagnosed with MS. They found the variant in all three they tested.
What they found was a genetic change known as a single nucleotide polymorphism, or SNP - a change in a single base-pair of the DNA - in a gene called STK11, which plays a role in tumor suppression and is believed to have several roles in brain function.
Genetic factors are known to influence the risk of developing MS. The UIC researchers were led to this variant thanks to a woman participating in another study at UIC. In a casual conversation, the woman told study coordinator Anne Boullerne that she and her four siblings - three sisters, including twins, and a brother - all had multiple sclerosis.
"This is an extremely rare occurrence," said Boullerne, who is research assistant professor of anesthesiology and lead author on the paper. She said she could find no published studies with five siblings with multiple sclerosis.
"I was immediately interested in the possibility of a genetic study of the family because all five siblings - an entire generation - are affected by MS, and so we could have a very good chance of discovering key genes related to inheritance of the disease."
The woman also described among her sisters and the women on her mother's side of the family a prevalence of diseases associated with Peutz-Jeghers syndrome, a rare genetic disorder caused by mutations in the STK11 gene and characterized by an increased risk for certain cancers, including breast, ovary and colon cancers.
A literature search by Feinstein uncovered an article that described how mice with a disabled STK11 gene had a higher incidence of loss of myelin from the nerves of the central nervous system - a defining characteristic of MS.
The woman consented to a complete DNA-sequencing of her genome. Boullerne took a close look at the STK11 gene, where she discovered the SNP. She next obtained consent to sequence the genomes of two of the woman's sisters and found they also carried the same SNP.
To determine if the SNP could be a contributing factor to the siblings' multiple sclerosis, the researchers screened DNA samples from 1,400 people - 750 with MS and 650 without - provided by Jorge Oksenberg at the University of California, San Francisco, who is a leading expert on the genetics of MS. They found that the SNP was 1.7 times as prevalent in women with MS as in women without the disease, making it one of the highest known genetic risk factors for MS.
Based on their analysis, the researchers estimate that the STK11 SNP is present in about 7 percent of the general population. But because far fewer people develop MS, other genetic or non-genetic factors must play a role in the development of the disease, Feinstein said.
Feinstein and Boullerne plan to continue their hunt for other genetic factors that may contribute to MS among the five siblings and possibly their parents. They will also investigate the function of the STK11 gene in the lab, which could reveal molecular pathways involved in multiple sclerosis.
Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (05/03/15)
The Journal of Neuroscience is reporting that a University at Buffalo researcher has discovered a way to keep remyelination going, using a drug that's already on the market.
According to scientists, there is a brief period after the myelin sheath has been attacked and damaged when it is able to repair itself, but this doesn’t last and the damage deteriorates further as someone with MS ages and their condition progresses.
“We have identified a new drug target that promotes stem cell therapy for myelin-based conditions such as MS,” says lead author Fraser J. Sim, PhD, assistant professor in the Department of Pharmacology and Toxicology in the University at Buffalo School of Medicine and Biomedical Sciences.
The study shows it is possible to boost myelination by targeting human oligodendrocyte progenitor cells with solifenacin, an anti-muscarinic drug that currently is approved and marketed to treat overactive bladder.
“Our hypothesis is that in MS, the oligodendrocyte progenitor cells seem to get stuck,” Sim explains. “When these cells don't mature properly, they don't differentiate into myelinating oligodendrocytes.”
In the new study, the approach Sim and his colleagues took was to first characterise the molecular pathways that govern the differentiation of human oligodendrocyte progenitor cells, and then identify drug candidates that would promote differentiation and myelin production.
They found that when a muscarinic type 3 receptor on human oligodendrocyte progenitor cells was activated, differentiation was completely blocked.
“So we thought, if we had something that blocks instead of activates this receptor, could we boost differentiation?” said Fraser. To do that, the researchers turned to solifenacin, the anti-muscarinic drug for overactive bladder; the bladder muscle contains several muscarinic receptors.
“We were excited about this because solifenacin is an approved drug that's already on the market,” said Sim.
To test whether the drug could boost myelin synthesis, the researchers transplanted human oligodendrocyte progenitor cells into mice that could not make myelin. The result was increased differentiation and myelin synthesis from the transplanted human cells.
However, Sim and his colleagues needed a functional endpoint, a way to know that the myelin being made was being translated into improved behaviour or function.
So Sim teamed up with Richard J. Salvi, PhD, SUNY Distinguished Professor in the Department of Communicative Disorders and Sciences, and director of UB's Center for Hearing and Deafness.
Together, they determined that an auditory brainstem response, which records brain wave activity in response to sounds, would be appropriate.
Sim said that it takes a certain amount of time for a signal to go from the ear to the front of the brain: “So in the readout, you get waves that should have a certain time pattern. When there isn't enough myelin, the signalling slows down. And if you add myelin, you should see the signals speed up.”
The tests showed improvement in the response to auditory signals in animals transplanted with the human oligodendrocyte progenitor cells treated with solifenacin.
“We have identified a way to improve human myelination,” said Sim.
The promising results have prompted Sim and his colleagues to seek funding for a small human trial. The study results are all preclinical and no human testing has been done yet.
The current study was funded by America’s National Multiple Sclerosis Society, the Kalec Multiple Sclerosis Foundation and the Empire State Stem Cell Fund.
In addition to Sim and Salvi, other co-authors are Kavitha Abiraman, Suyog U. Pol, Melanie A. O'Bara, Guang-Di Chen, Zainab Khaku, Jing Wang, David Thorn, Bansi H. Vedia, Exinne C. Ekwegbalu and Jun-Xu Li.
The new study adds to Sim's body of research on stem cells and myelination, which previously determined that a critical phase of remyelination fades with age.
Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (02/03/15)
A pioneering new stem cell treatment is allowing people with multiple sclerosis to walk, run and even dance again, in results branded ‘miraculous’ by doctors.
Patients who have been wheelchair-bound for 10 years have regained the use of their legs in the groundbreaking therapy, while others who were blind can now see again.
The treatment is the first to ‘reverse’ the symptoms of MS, which has no cure, and affects around 100,000 people in Britain.
The two dozen patients who are taking part in the trials at the Royal Hallamshire Hospital in Sheffield and Kings College Hospital, London, have effectively had their immune systems ‘rebooted’.
Although it is unclear what causes MS, some doctors believe that it is the immune system itself which attacks the brain and spinal cord, leading to inflammation and pain, disability and in severe cases, death.
In the new treatment, specialists use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patient’s own blood.
Stem cells are so effective because they can become any cell in the body based on their environment.
"Since we started treating patients three years ago, some of the results we have seen have been miraculous," Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, told The Sunday Times.
"This is not a word I would use lightly, but we have seen profound neurological improvements."
During the treatment, the patient's stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.
The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.
Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.
Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two, but she claims the new treatment has transformed her life.
“It worked wonders,” she said. “I remember being in the hospital... after three weeks, I called my mum and said: 'I can stand'. We were all crying.
"I can run a little bit, I can dance. I love dancing, it is silly but I do. I enjoy walking my daughter around the park in her pram. It is a miracle but I can do it all."
However specialists warn that patients need to be fit to benefit from the new treatment.
"This is not a treatment that is suitable for everybody because it is very aggressive and patients need to be quite fit to withstand the effects of the chemotherapy," warned Prof Sharrack.
Charities welcomed the research but also urged caution.
Dr Sorrel Bickley, Research Communications Manager at the MS Society said: “This new study reports very encouraging findings, which add to a growing body of research into stem cell transplantation in MS. However, there are limitations to how we can interpret these results because there was no control group used, which means we can’t be sure the results are robust.
"Momentum in this area of research is building rapidly and we're eagerly awaiting the results of larger, randomised trials and longer term follow up data.
“New treatments for MS are urgently needed, but as yet there are no stem cell therapies licensed for MS anywhere in the world. This means they aren't yet established as being both safe and effective. This type of stem cell therapy is very aggressive and does carry significant risks, so we would strongly urge caution in seeking this treatment outside of a properly regulated clinical trial."
The research was published in the Journal of the American Medical Association.
Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (02/03/15)
MS-UK launches live web chat service to support anyone affected by multiple sclerosis after seeing a 23% increase in contact(02/03/15)
MS-UK, the national charity supporting anyone affected by multiple sclerosis to make the most of today, has launched a live web chat feature on its website at www.ms-uk.org/livewebchat.
MS-UK has launched the new web chat service to support more people affected by MS. Between 2013 and 2014, the charity experienced a 23% increase in the amount of people who use the MS-UK Helpline. In January 2015 the MS-UK Helpline supported 32% more people compared to January 2014.
Amy Woolf, CEO of MS-UK, says ‘By launching the live web chat service, we hope to offer people another channel to connect with trained MS Advisors. Not everybody likes talking on the telephone, but they still want an instant response to their concerns. The growth we have seen in the past 12 months of people wanting information and support about multiple sclerosis tells us we’re doing the right thing.’
Since 1993, MS-UK has offered information and support to anyone affected by multiple sclerosis via telephone. The MS-UK Helpline is confidential, unbiased and completely free.
At MS-UK we are dedicated to giving support and information to anyone affected by MS. We offer a range of services including our Helpline, publishing New Pathways magazine and access to our Wellness Studio at Josephs Court, MS-UK Centre of Excellence.
Find out more about MS-UK online at www.ms-uk.org
Source: MS-UK (02/03/15)
People who drink four to six cups of coffee a day may be less likely to get multiple sclerosis, US and Swedish researchers say.
While caffeine intake has been associated with a reduced risk of Parkinson's and Alzheimer's diseases, the findings of the research show the same could apply to MS.
“Our study shows coffee intake may also protect against MS, supporting the idea the drug may have protective effects for the brain,” said lead author Ellen Mowry of Johns Hopkins University School of Medicine.
The findings of twin US and Swedish studies compared more than 1,000 MS patients with a similar number of healthy people.
Researchers tracked how much coffee the subjects drank in the one, five and 10 years before symptoms began for those affected by MS.
After accounting for other factors such as age, sex, smoking, body mass index and sun exposure, the Swedish study found “compared to people who drank at least six cups of coffee a day during the year before symptoms appeared, those who did not drink coffee had about a 1½ times increased risk of developing MS”.
Similar protective effects were seen among those who drank lots of coffee five to 10 years before symptoms appeared.
The US study found “people who didn't drink coffee were also about 1½ times more likely to develop the disease than those who drank four or more cups of coffee per day in the year before symptoms started to develop”.
More research is needed to determine if caffeine has any impact on relapse or long-term disability due to MS.
Source: The Sydney Morning Herald © 2015 Fairfax Media (27/02/15)
Oral feeding of cinnamon is capable of suppressing multiple sclerosis (MS) in mice models, according to research published in PLOS One.
Researchers from the Rush University Medical Center in Chicago examined the effects of various household spices on mice models of MS, in accordance with a $750,000 grant they were awarded by the National Institutes of Health in 2011. The mice were introduced to the model of MS, called experimental allergic encephalomyelitis (EAE) in mice, and were randomly placed on a scale from 0 = no disease to 5 = moribund. The cinnamon was introduced as a powder in 0.5 percent methylcellulose (MC) and EAE mice were given 100 µL cinnamon mixed MC powder once daily using a needle. After an observation period of 14 days post immunisation (dpi), 5 mice per each group were anesthetized and their spinal cords were evaluated for inflammation.
Ceylon cinnamon (Cinnamonum verum), the researchers found, was much more pure than Chinese cinnamon (Cinnamonum cassia), and so it was used in the study. Both are widely available for sale in the United States, the authors commented. Cinnamon, the researchers continued, has a long history of being used medicinally, including for treatments of arthritis, coughing, hoarseness, sore throats, and the like.
Less than half (40 percent) of mice developed EAE, and the EAE mice were treated with different doses of cinnamon powder from 8 dpi. Cinnamon significantly inhibited clinical symptoms, and no decrease in disease incidence was observed at a dose of 25 mg/kg body wt/d. At an increased dose of 100 mg/kg body wt/d, there was a very significant inhibition of clinical symptoms accompanied by a reduction in disease incidence.
“These results clearly demonstrate that cinnamon can ameliorate the ongoing relapsing remitting EAE when administered either early (at the onset of acute phase) or late (at the onset of relapsing disease),” the researchers described an additional result of the study.
The blood brain barrier (BBB) and blood spinal cord barrier (BSB) were also preserved after the treatment of cinnamon in transgenic mice. The investigators used infrared dye in EAE mice and tracked its spread, noting that the dye was strongly inhibited in mice who received the cinnamon treatment. In a similar analysis, the researchers discovered that the cinnamon treatment inhibited infiltration of mononuclear cells, inflammation, and demyelination in the spinal cord of EAE mice.
“These results highlight a novel immunomodulatory role of cinnamon and suggest that this widely-used spice may be explored for therapeutic intervention in MS,” the researchers concluded.
In July 2014, Rush similarly announced that cinnamon can also slow the effects of Parkinson’s Disease as well, citing the effects cinnamon has on the body once it is metabolised.
Source: MD All Specialities Copyright 2015 MJH Healthcare Holdings, LLC (25/02/15)
Researchers in Spain have conducted a landmark study to shed light on how marijuana reduces the activity of motor neurons that lead to symptoms such as muscle weakness in people with MS.
Researchers at the University of Cadiz, led by Professor Bernardo Moreno, used synthetic analogues of the psychoactive compounds of marijuana to see how they affected motor neurons.
They looked, in particular, at movements of the tongue and how they responded to the drug.
'During the investigation, we used an animal model in which we studied the alterations produced by synthetic cannabinoids on the activity of the motor neurons,' the researchers wrote.
'In doing so, we discovered that these psychoactive compounds inhibit the information that reaches these neurons via the synapses.
'In other words, cannabinoids hinder the transmission of information between neurons.'
All of this could lead to problems speaking, breathing and swallowing food.
But the same reaction could also explain the beneficial effects that marijuana has on people with neurodegenerative diseases such as multiple sclerosis.
The scientists say that by reducing motor neuron activity, people with multiple sclerosis may have temporary relief from their symptoms.
Source: Daily Mail Online © Associated Newspapers Ltd 2015 (24/02/15)
A recent study led by researchers at the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada, revealed a promising new method for MS treatment. The study was published in the journal Annals of Clinical and Translational Neurology and is entitled “Blocking GluR2–GAPDH ameliorates experimental autoimmune encephalomyelitis.”
MS is a progressive, immune-mediated disorder in which the body’s own immune system attacks the central nervous system (brain and spinal cord nerves). The exact causes for MS are not clear but the fact that the immune system is involved makes it a target for current therapies that address immune system responses. While the medications used in these therapies are not curative, they can help relieve the disease symptoms and slow its progression.
Researchers have identified a previously unknown spinal cord alteration linked to MS related to a protein called GAPDH (glyceraldehyde 3-phosphate dehydrogenase, a protein important in glucose metabolism) and a specific cell receptor for the glutamate neurotransmitter (the major excitatory neurotransmitter in the brain, critical for normal brain function). GAPDH was found to interact with this glutamate receptor, called the AMPA receptor, at higher levels in post mortem spinal cord tissues of MS patients and also in MS animal models. The AMPA receptor has been previously suggested as being able to mediate the cytotoxicity linked to the loss of neurons. Researchers therefore hypothesized that blocking AMPA-GAPDH interactions could be therapeutic for MS.
“We’ve identified a new biological target for MS therapy,” said the study’s senior author Dr. Fang Liu in a news release. The team discovered an approach to changing this alteration in order to stop nerve cell damage and also improve motor problems usually linked to the disorder. They developed a new peptide (a small piece of protein) to block the interaction between GAPDH and the AMPA receptor, more specifically GAPDH -GluR2 subunit of the AMPA receptor, and tested it in MS animal models.
“We found that our peptide disrupted this linkage, and led to major improvements in neurological functioning,” explained Dr. Liu. Mice treated with the peptide had their motor function significantly improved and a lower rate of neuron death along with myelin restoration, the protective coating of neurons important for the normal transmission of nerve impulses. More importantly, the peptide developed was found to be different from drugs targeting the glutamate system as it did not directly suppress the immune response of the body, which is a common side effect of many glutamate drugs.
The team believes that the GluR2-GAPDH complex could be a novel target for the development of new types of MS therapies that exploit a different mechanism from those currently used in treatments. “Our priority now would be to extend this research and determine how this discovery can be translated into treatment for patients,” concluded Dr. Liu.
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (23/02/15)
A study published by a team of investigators at the University of Tokyo’s Institute of Medical Science and Osaka University’s Graduate School of Engineering has presented new evidence demonstrating how Toll-like receptor 9 (TLR9) binds to pathogenic DNA, turning on the functions of the innate immune system. This novel discovery is important for the design of new therapeutic drugs for autoimmune diseases, such as multiple sclerosis (MS), targeting TLR9. The study was published in the new issue of Nature.
Toll-Like Receptors (TLRs) play a critical role in the early innate immune (non-specific first line of defense against pathogens) response to invading bacteria, viruses, and other foreign agents and are also involved in sensing the body’s internal alarm system to help activate other important components of its immune defenses. TLR9 detects the alarm system by recognizing a DNA sequence called Cytosine-phosphate-Guanine dinucleotide (CpG), a pattern that is specific to bacteria and viruses. This induces the release of interferon (IFN) and initiates the inflammatory response process. For autoimmune disease such as MS, studies have shown that TLRs and the release of IFN play a major role in the initiation of disease, triggering of relapses and regulation of damage.
Unfortunately, the exact structure of TLR9 and how it functions remained unknown, inhibiting advancement of treatments that specifically targeted these receptors. This study conducted by Professor Toshiyuki Shimizu PhD’s research group used crystallographic (molecular structure) data to evaluate TLR9’s ring-shaped form in three crucial states: as a free protein, bound to an inhibitor DNA, and bound to an agonist DNA. In the first two cases, TLR9 exists as a single ring, but when it binds to an agonist, like a DNA segment containing the CpG motif, two of its rings are bound together and form a dimer (chemical structure formed from two similar sub-units) that shares two DNA molecules.
In a statement explaining the importance of the study findings, Professor Shimizu said, “TLR9 is a promising drug target for treating viral infections, cancer, autoimmune diseases, and so on, so researchers have been trying to elucidate structurally how TLR9 recognizes pathogenic DNA ever since it was discovered more than a decade ago. This work represents a big step forward for drug development targeting TLR9, and also for our understanding of nucleic acid sensing by TLR9. TLRs have received significant attention due to their critical roles in the innate immune system, and our group has been focusing on the structural study of TLRs for many years. We believe that a precise understanding of TLR function should come from its visualization by structural analyses. Actually, we were quite surprised at the result of this study: the two DNA molecules, agonist and inhibitor, bound to completely different sites on TLR9, and the DNA molecules themselves had completely different structures, both of which we could never have predicted.”
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (20/02/15)
Due to its complex nature, scientists have only really been unravelling the mysteries of the brain over the last few decades, and now researchers have discovered that the brains of mice contain at least seven unknown types of cells, including a nerve cell.
These findings could shed light on conditions such as multiple sclerosis.
Using a process called single cell sequencing, scientists at the Karolinska Institute in Sweden produced a detailed map of brain cell types and the genes active within them.
It is the first time the method has been used on such a large scale and on such a complex tissue.
Researchers studied more than 3,000 cells, one at a time, to identify a number of previously unknown types.
‘If you compare the brain to a fruit salad, you could say that previous methods were like running the fruit through a blender and seeing what colour juice you got from different parts of the brain,’ said Sten Linnarsson, senior researcher at the Department of Medical Biochemistry and Biophysics.
‘But in recent years we've developed much more sensitive methods of analysis that allow us to see which genes are active in individual cells.
‘This is like taking pieces of the fruit salad, examining them one by one and then sorting them into piles to see how many different kinds of fruit it contains, what they're made up of and how they interrelate.’
After the scientist analysed the 3,000 cells from the cerebral cortex in mice, they compared which of the 20,000 genes were active in each one, enabling them to sort the cells into virtual piles.
They identified 47 different kinds of cell, including a large proportion of specialised neurons, as well as blood vessel cells and glial cells, which take care of waste products, protect against infection and supply nerve cells with nutrients.
Then, they identified unknown cell types, including a nerve cell in the outermost layer of the cortex plus six different types of oligodendrocyte.
These are cells that form the electrically insulating myelin sheath around the nerve cells.
The study, published in the journal Science, could shed more light on things that affect the myelin.
Co-leader of the study, Jens Hjerling-Leffler, said: ‘We have created a much more detailed map of the cells of the brain that describes each cell type in detail and shows which genes are active in it.
‘This gives science a new tool for studying these cell types in disease models and helps us to understand better how brain cell respond to disease and injury.’
Source: Daily Mail Online © Associated Newspapers Ltd 2015 (20/02/15)
Women with multiple sclerosis (MS) may have lower levels of important antioxidant and anti-inflammatory nutrients, such as folate from food and vitamin E, than healthy people, according to a new study released today that will be presented at the American Academy of Neurology's 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.
For the study, researchers identified 27 Caucasian women with MS and compared them to 30 healthy Caucasian women between the ages of 18-60 and with body mass index of less than or equal to 30 kg/m2. Participants reported on their diet and nutrition over the previous year prior to starting vitamin D supplementation.
On average, the women who had MS had lower levels of five nutrients with antioxidant or anti-inflammatory properties: food folate, vitamin E, magnesium, lutein-zeaxanthin and quercetin. For food folate, the women with MS had average intake of 244 micrograms (mcg), while the healthy women had an average intake of 321 mcg. The recommended daily allowance is 400 mcg. For magnesium, the women with MS had average intake of 254 milligrams (mg), while the healthy women met the recommended daily allowance of 320 mg with an average of 321 mg. The women with MS also had a lower average percentage of their calories from fat than the healthy participants.
"Since MS is a chronic inflammatory disorder, having enough nutrients with anti-inflammatory properties may help prevent the disease or reduce the risk of attacks for those who already have MS," said study author Sandra D. Cassard, ScD, with John Hopkins University in Baltimore, MD. "Antioxidants are also critical to good health and help reduce the effects of other types of damage that can occur on a cellular level and contribute to neurologic diseases like MS. Whether the nutritional differences that we identified in the study are a cause of MS or a result of having it is not yet clear."
The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS).
Source: EurekaAlert! Copyright © 2015 by the American Association for the Advancement of Science (AAAS) (20/02/15)
Early research shows results for ‘vaccine’ (18/02/15)
In April 2010, sipuleucel-T (Provenge) became the first dendritic cell vaccine in cancer treatment to be approved by the US Food and Drug Administration (FDA), and the agent is now used in the treatment of metastatic castration-resistant prostate cancer. Insights gleaned from this research are now being applied in the study of a potential vaccine for multiple sclerosis (MS) treatment and prevention.
“We discovered DC-ASGPR, one of the receptors expressed on human dendritic cells, has novel functions to promote antigen-specific regulatory T cells that can efficiently suppress inflammatory responses,” said principal investigator SangKon Oh, PhD, from the Baylor Institute for Immunology Research, in a press release. “This prompted us to test our discovery in autoimmune diseases where antigens are known.”
Traditional treatments for MS may trigger immune system–related side effects and adversely affect the immune system even though they demonstrate efficacy. Oh launched lab research 3 years ago along with colleagues Gerard Zurawski, PhD, and Ted Phillips, MD, PhD, using a significantly different approach.
“Oh’s approach is a very unique effort that would harness one’s own immune system to suppress MS in an auto antigen–specific manner without disrupting other aspects of normal immunity,” said Phillips, a neurologist whose work has focused on MS for more than three decades. Results have been positive, according to Oh, who said they are hopeful this study can enter a phase I clinical trial within the next three years. Researchers will also apply these findings to future studies about dendritic cell vaccines, including a planned research effort for type 1 diabetes mellitus.
“We need new treatments that, while highly efficacious, also minimally adversely impact the individual’s immune system,” Phillips said.
Source: HCPLive Copyright HCPLive 2006-2015 Intellisphere, LLC (18/02/15)
A team of scientists have uncovered a molecule that fights one of the main causes of inflammatory diseases and could be the key to improved treatments for diseases like Alzheimer's, arthritis and multiple sclerosis. The research team, led by Trinity and the University of Queensland Australia, showed the molecule, MCC950, could suppress the key activator in inflammatory diseases, NLRP3. The finding also confirms that inflammatory diseases all share a common process, even though the part of the body becoming inflamed might differ.
Researcher Luke O'Neill said drugs like aspirin or steroids can work in several diseases, but can have side effects or be ineffective, and what they have found is a potentially transformative medicine, which targets what appears to be the common disease-causing process in a myriad of inflammatory diseases. There is huge interest in NLRP3, both among medical researchers and pharmaceutical companies, and they feel their work makes a significant contribution to the efforts to find new medicines to limit it. MCC950 can be administered orally and will be cheaper to produce than current protein-based treatments, which are given daily, weekly, or monthly by injection.
More importantly, the new molecule also remains in the body for a shorter duration, allowing clinicians to stop the anti-inflammatory action of the drug if the patient ever needed to switch their immune response back to 100 percent, in order to clear an infection. So far, the results have shown great promise for blocking multiple sclerosis in a model of the disease, as well as in sepsis where, in response to bacteria, potentially fatal blood poisoning occurs. However, the target for MCC950 is strongly implicated in diseases such as Alzheimer's disease, atherosclerosis, gout, Parkinson's disease and rheumatoid arthritis, which means it has the potential to treat all of these conditions. The study is published in medical journal Nature Medicine.
Source: dna © 2015 Diligent Media Corporation Ltd (18/02/15)
In a study published in the journal Clinical Chemistry and Laboratory Medicine, investigators Moccia et al identified uric acid as a potential biomarker in the progression of multiple sclerosis-related disability.
Uric acid, which has activity as a natural scavenger of oxygen radicals, is present in the bloodstream as a breakdown product of purines (adenine and guanine). In animal studies, uric acid has been shown to have some potential as a treatment for MS. Results of these studies led investigators in the CCLM study to search for a relationship between MS severity and levels of uric acid. In the case-control study, using propensity score matching, investigators paired 362 patients with MS and 181 control individuals without MS.
To reduce variation between populations, investigators corrected data for patient age, gender, and kidney function. Upon regression analysis, investigators identified a significant association between low levels of serum uric acid among patients with MS compared with controls, with an R-squared value of 30.4 per cent and significance determined at a P value level of 1.4 per cent.
Longer disease duration was associated with a longer time from diagnosis and a higher Expanded Disability Status Scale (EDSS) score (P < .001, all comparisons). These findings suggest that uric acid levels may be a biomarker of MS disability and progression, even though previous studies suggest that uric acid may have a limited role as a disease marker and as a therapeutic target in MS.
For example, a 2006 analysis, published in the journal Clinical Neurology and Neurosurgery, found that uric acid levels did not change as a result of immunomodulatory or immunosuppressive drug treatment in patients with MS.
In addition, in the Association of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial, investigators administered a precursor of uric acid — inosine — to patients with MS in conjunction with interferon-beta over the course of two years. The results of this trial were negative, and uric acid did not have any additional benefit on disability outcomes versus interferon-beta alone.
Despite the negative result of the ASIIMS trial, antioxidative drugs may have a future in treatment of MS. However, uric acid may be a biomarker — not a treatment modality. Studying uric acid may help physicians predict the progression of MS in patients, although previous research indicates that uric acid levels do not predict response to treatment, and supplementation with uric acid does not alter the progression of disability in MS. Further study will be necessary to determine whether or not drugs that mimic the effects of uric acid are of any value.
Source: HCPLive Copyright HCPLive 2006-2013 Intellisphere, LLC (18/02/15)
Oral regimen ‘delays onset of MS’(17/02/15)
For the first time, an oral therapy has been proven to reduce the risk of developing clinically definite multiple sclerosis in patients with a clinically isolated syndrome. In a phase III trial published in the journal Lancet Neurology, Miller et al clarified the role of teriflunomide (Aubagio) in the treatment of early episodes of demyelinating symptoms suggestive of MS.
This randomized, double-blind, placebo-controlled study, known as the TOPIC study, evaluated the safety and efficacy of teriflunomide for patients between 18 and 55 years of age who had experienced their first instance of a clinically isolated syndrome in the 90 days prior to randomization in the trial. Each patient involved in the study was required to have at least 2 MRI-determined lesions (measured using T2-weighted MRI) at least 3 mm in diameter.
Investigators assessed the amount of time between the initial neurologic event and any new neurologic event — an event that would mark the transition from a clinically isolated syndrome to clinically definite MS (CDMS). Secondarily, investigators assessed MRI outcomes, including occurrence of new gadolinium-enhancing or T2 lesions. The study used an intent-to-treat design, but excluded from the study two patients who were randomized to receive teriflunomide but never received a dose of study medication.
Two different regimens of daily teriflunomide significantly reduced the risk of conversion to CDMS. The 7-mg dose reduced the risk of developing CDMS by 31.4 per cent, and the 14-mg dose reduced the risk of developing CDMS by 34.9 per cent.
Adverse events (AEs) occurring in the trial included increased liver enzyme levels, hair thinning, diarrhea, paresthesia, and upper respiratory tract infection. Each of these AEs occurred in at least 10 per cent of patients using teriflunomide, and occurred at a rate at least two percentage points higher than in patients receiving placebo.
Serious AEs included increased liver enzyme levels, which occurred in two per cent of each treatment group—including the placebo group.
The TOPIC study is the first to evaluate the efficacy of an oral treatment in reducing the risk of progression from a clinically isolated demyelinating syndrome to clinically definite MS.
Source: HCPLive Copyright HCPLive 2006-2013 Intellisphere, LLC (17/02/15)
A recent study found that patients taking dimethyl fumarate (Tecfidera) had low counts of CD8+ T cells, though their overall levels of lymphocytes were within the normal range. The findings suggest that doctors may want to monitor specific lymphocyte levels in addition to doing full blood cell counts.
In November 2014, Biogen Idec confirmed its first case of progressive multifocal leukoencephalopathy (PML), a rare brain infection, in a patient taking dimethyl fumarate (Tecfidera), and complications from the infection resulted in the patient’s death. The news sparked a warning from the U.S. Food and Drug Administration and concern from both patients and physicians about how to prevent another case of PML.
Research from the University of California, San Francisco (UCSF), may provide some insight on better monitoring techniques for patients taking dimethyl fumarate (DMF). In a paper published in Neuroimmunology & Neuroinflammation (Spencer et al., 2015), researchers followed 14 patients every three months for a year and examined levels of leukocyte and lymphocyte subsets including CD3+, CD4+, CD8+ T cells, CD19+ B cells, and CD56+ natural killer cells.
They found that total leukocyte and lymphocyte levels diminished by the 6-month mark and that half the patients had leukocyte levels below the lower limit of normal. While the levels of all the cell subsets dropped over time, the researchers noted a particularly striking decrease in the level of CD8+ T cells, which are primarily involved in responding to viral infection.
PML develops from an opportunistic virus called the John Cunningham virus. DMF comes with a recommendation that physicians take blood cell counts of patients before starting on the drug and annually or as clinically necessary afterward. The safety precautions recommend that physicians consider interrupting treatment if lymphocyte counts decrease below 500 cells/μL in the blood and the low levels persist for six months. The label also says patients should stop taking DMF if any symptoms of PML occur, which include “clumsiness; progressive weakness; and visual, speech, and sometimes personality changes,” according to the National Institute of Neurological Disorders and Stroke. The symptoms of PML can also develop slowly over the course of weeks to months.
Typically, cell counts look at the major types of blood cells (red blood cells, lymphocytes, and leukocytes) but do not look at subsets. What the UCSF team found was that patients may have dangerously low levels of cell subsets, like CD8 cells, while still having total leukocyte and lymphocyte counts within the normal range.
“[CD8+ T cells] are the cells that are very important in antiviral immunity,” corresponding author Scott Zamvil, M.D., Ph.D., of UCSF told MSDF. Without the CD8+ T cells, the JC virus that leads to PML may be more able to infiltrate the body while the immune system has its guard down. But due to the small sample size and the relative short duration of the study, Zamvil said the results are not yet definitive. “So we need more investigation. These results are cautionary.”
Zamvil also said that the investigators did not take biopsies of the brain or lymph nodes, which may have different cell levels that could affect a patient’s susceptibility to or protection from PML. But due to the nature of the results, Zamvil told MSDF that he and his colleagues felt it important to get their data out there so that clinicians can make use of it.
Source: Multiple Sclerosis Discovert Forum Copyright © 2014 MGH and ACP (13/02/15)
New treatment for MS fatigue suggested(12/02/15)
The Multiple Sclerosis Journal has published the results of a study by researchers from Israel who measured the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue.
Fatigue is one of the most common and disabling symptoms of multiple sclerosis, occurring in up to 90 per cent of people with MS.
MS-related fatigue is not directly linked to depression or degree of neurological disability, and may occur first thing in the morning even if the patient has slept well.
At the moment, there is no medication approved specifically to treat MS-related fatigue. Amantadine was the first medication used to treat fatigue, although most studies have not shown evidence of benefit. Modafinil was studied recently, also showing inconsistent results.
Several non-drug interventions have also been proposed including aquatic exercise training, occupational therapy, and internet-based programs.
Combating MS-related fatigue is of importance to those affected by MS, as it interferes with daily living, work, family life and socialising.
In the study, 158 MS patients with significant fatigue received Alfacalcidol or a placebo.
The researchers found Alfacalcidol is a safe and effective treatment for fatigue among patients with MS.
These findings suggest that Alfacalcidol, a drug similar to vitamin D, should be considered a safe treatment option for MS-related fatigue.
Source: Multiple Sclerosis International Federation (12/02/15)
Research breathes new life into theory supporting possible viral etiology of multiple sclerosis(11/02/15)
Several clusters of multiple sclerosis cases have been identified around the world, some of which have occurred in association with exposure to infectious agents, while others have suggested an influence of environmental toxins, such as heavy metals.
Although MS is likely a result of multifactorial influences, there is some evidence that viruses play a role in the disease. For example, in the Faroe Islands, which lie northwest of Scotland and halfway between Iceland and Norway, native residents began to develop MS starting in 1943 after British occupation of the island during World War II. Although no virus was ever identified, John F. Kurtzke, MD, creator of the Kurtzke Expanded Disability Status Scale, said he believes the Faroe Island cluster suggests a viral etiology of MS.
In a scientific paper published in 2013 in the journal Brain, Kurzke wrote, “As of 1999, we had found 189 suspected cases, and we had agreed that 83 of them were examples of MS… There is no evidence that MS occurred among native-born resident Faroese before July 1943, when symptoms began in one patient… The abrupt onset indicates that the disorder had to have been introduced into the islands at a single time.”
In later research, Kurtzke, who is professor emeritus at Georgetown University in Washington, DC, identified similar patterns of MS incidence in Iceland and the Shetland-Orkney islands.4 Kurtzke and colleagues also examined the prevalence of MS in populations migrating from equatorial regions (where the prevalence of MS is low) to higher latitude regions (where the prevalence of MS is higher). From these studies, Kurtzke concluded that MS may be partly caused by a virus acquired before the age of 15 years, which may then lead to MS symptoms after a delay of 15 to 20 years.
Adding to the knowledge base developed by Kurtzke about the relationship between MS and viruses, Julian Gold, MBBS, MD, of the Albion Street Centre in Sydney, Australia, and colleagues studied the link between MS and human immunodeficiency virus (HIV). HIV and MS are both well-characterized conditions, although they rarely occur in the same patient.6 In 1996, Gold noticed that one of his patients who had both MS and HIV experienced a reduction in symptoms after starting antiretroviral therapy. Over 12 years of therapy, the patient continued to experience few symptoms of MS. Based on this case, Gold hypothesized that the antiretroviral medication, the immunosuppression associated with HIV, or both, might slow the progression of MS.
To evaluate the hypothesis, researchers in Denmark studied the incidence of MS in patients with HIV. Investigators followed 5018 patients with HIV over a median of 5.2 years and compared those results with a control population of 50,149 MS-free individuals who were followed for a median of 7.6 years.
Seven cases of MS were observed in patients with HIV, even though approximately 18 cases would be expected in a comparable group of patients without HIV. The relative risk of developing MS was significantly lower among patients with HIV, with new cases of MS occurring at more than one-third (38%; 95% confidence interval [CI]: 15%-79%) the rate observed in the general population.
In a secondary analysis, investigators analyzed MS cases that were identified in patients 1 year or more after they acquired HIV. A total of 3 such cases were identified. Although this number was smaller than the expected number of 13 cases of HIV that would be expected to occur in a similar population without HIV, the result was no longer statistically significant (hazard ratio: 0.25; 95% CI: 0.07-0.65). The lack of statistical significance may be a result of the small number of MS cases observed in patients with HIV.
According to Gold, who presented his research in MS at the Barts and London School of Medicine and Dentistry on MS Research Day in 2013, “As a result of these observations, we are now launching a unique clinical trial … the INSPIRE trial.” This trial will begin with a pilot phase in which patients with RRMS will receive raltegravir over a 3-month baseline period and a 3-month treatment period. Patients will be evaluated for the primary outcome of new gadolinium-enhancing lesions.7,8 Gold compares the pathophysiology of MS with a car lying in pieces: “It’s very complicated…all over the world there are researchers working on little bits to do with MS. Some are working on vitamin deficiencies, and others are working on Epstein-Barr virus (EBV), and others are working on hypoxia, but nobody has been able to put all these pieces together and drive it away.”
The pathophysiology of MS is very complex and the involvement of viruses is far from certain. For now, the use of antiviral agents in patients with MS should be limited to the clinical trials setting.
Source: HCP Live © HCP Live (11/02/15)
Several renowned scientists working on multiple sclerosis (MS) recently joined forces to discuss and highlight the progress and knowledge gaps related to MS research, the prospects of finding a cure for the disease, and a strategy to reduce the burden the disease places on patients.
A series of articles was published by the researchers in the February issue of the Lancet Neurology journal and stress the need for better diagnosis and MS treatments.
Authors from different academic fields who share the same interest in MS research have outlined a state-of-the-art plan for MS investigation and updated information on what causes the disease to progress, its mechanisms, and the development of novel methods to conduct clinical trials.
The first article is focused on recent data concerning nervous system damage leading to progressive disability in MS, and calls for increased insight into the causes of MS disease progression. The authors Don Mahad from the University of Edinburgh, Bruce Trapp from the Cleveland Clinic, and Hans Lassmann from the Medical University of Vienna explained that progressive damage can be either caused by oxidative injury (derived from normal byproducts of bodily processes called free radicals) or by injuries to mitochondria, which are the energy-producing organelles inside cells.
In addition, the authors state that both type of injuries, believed to be initiated by MS attacks, are amplified due to alterations throughout patients’ lives. Even though there is an increased understanding about the mechanisms behind MS, there are still not enough models of the chronic stages of injuries related to the disease.
Treating symptoms related to MS and rehabilitating patients with them requires the evaluation of new therapies in clinical trials. Anthony Feinstein from the University of Toronto, Jenny Freeman from Plymouth University, and Albert Lo from Brown University believe that overall there have been too few studies involving only people with progressive MS, and as a result there is a lack of disease-modifying therapies for progressive stages of the disease.
Additionally, Jeremy Chataway from University College London, along with Daniel Ontaneda and Robert Fox, both from the Cleveland Clinic, debate the problem of negative results from phase III trials to evaluate new therapies in progressive MS patients. The authors provide a series of lessons and strategies to improve results, such as applying improved clinical measures of effectiveness, better trial designs, and the use of advanced imaging tools and spinal fluid biomarkers to better understand treatment benefits.
Finally, Timothy Coetzee from the National MS Society, Paola Zaratin from the Italian MS Foundation, and MS blogger Trevis Gleason give insights on the need for research partnerships, regulatory innovations, and more sustained funding for research. They also evaluate the work of the international organization Progressive MS Alliance, which has recently opened a second request for research proposals, encouraging international research partnerships. The organization has been dedicated to funding and supporting research in order to improve the lives of MS patients.
“Every time a new treatment for RRMS comes on the market, it serves to remind people with progressive multiple sclerosis that they are still waiting,” stated Alan Thompson from the University College London in his article on new MS therapies. The authors believe it is crucial to understand what causes the development of progressive MS, as well as to innovate clinical trial design.
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (12/02/15)
New research found statistically significant correlations between MRI measures of the spinal cord, optical coherence tomography measures of the retina, and clinical disability.
Two common categories of multiple sclerosis symptoms, visual and sensorimotor, are associated with lesions in the spinal cord (SC) and optic nerve. The symptoms also co-occur frequently in specific classes of demyelinating diseases such as neuromyelitis optica. Researchers from Johns Hopkins University recently tested for a relationship between the two central nervous system structures (Oh et al., 2015).
The team conducted MRI scans of the spinal cord and optical coherence tomography scans of the retinas of 11 healthy controls and 102 patients with MS: 66 relapsing-remitting and 36 progressive. They assessed the participants for visual acuity and sensorimotor dysfunction, and then looked for statistical associations between scans and clinical phenotype.
In a univariate analysis the investigators found several SC-related measures were associated with the peripapillary retinal nerve fiber layer (pRNFL). Incorporating those factors into a multivariate statistical model that controlled for age, sex, and prior optic neuritis, the team then analyzed SC cross-sectional area (SC-CSA), pRNFL, and brain parenchymal fraction . They found that SC-CSA and pRNFL independently correlated with multiple clinical measures. Specifically, both measures had statistically significant associations with low-contrast visual acuity, high-contrast visual acuity and vibration sensation threshold. Additionally, SC-CSA had a significant association with Expanded Disability Status Scale, but pRNFL did not associate with EDSS.
The study adds credence to the intuitive notion that MS has global effects on the central nervous system (CNS). Rather than causing damage in the brain alone, the disease affects all areas of the CNS and, as these data suggest, damage in the SC and optic nerve may be more closely associated with specific clinical symptoms of MS than with brain damage and atrophy.
But the study also had its limitations. The control group was rather small, and though 102 MS patients is a reasonable cohort size, the statistical power dwindles when they are examined by relapsing and progressive subgroups.
In the article, the authors suggest that in the future, SC and retinal scans may supplement brain scans to illuminate causes for specific variations in clinical disability. If their findings are validated, they went on to write, the approach would also better researchers’ understanding of the disease course and progression.
Source: Multiple Sclerosis Discovery Forum Copyright © 2014 MGH and ACP (12/02/15)
Multiple sclerosis patients who had autologous hematopoietic stem-cell transplantation had significantly fewer new lesions on MRI than those on mitoxantrone, Italian researchers have found.
In a randomized, controlled trial, CD34-positive hematopoietic cell transplant reduced the number of new T2 lesions by 79 per cent compared with mitoxantrone over a four-year study period, Giovanni Mancardi, MD, of the University of Genova in Italy, and colleagues reported in Neurology.
The therapy also reduced gadolinium-enhancing lesions and annualized relapse rate, but there was no difference in progression of disability, although the study was not powered to look at the latter finding, the researchers noted.
"More research is needed with larger numbers of patients who are randomized to receive either the stem-cell transplant or an approved therapy, but it's very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that are not responding well to standard treatments," Mancardi said in a statement.
The ASTIMS study enrolled 21 patients from seven centers in Italy and Spain from 2004 to 2009 who had relapsing-remitting or secondary progressive MS. They were randomized to intensive immunosuppression followed by either mitoxantrone or autologous hematopoietic stem-cell transplantation every month for 6 months.
The intensive immunosuppression regimen involved mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine arabinoside, etoposide, melphalan, and anti-thymocyte globulin.
The mean age at transplantation was 35.5 years, and the median Expanded Disability Status Scale (EDSS) score at baseline was 6.
ASTIMS was designed as a phase III study, but became a phase II trial with a primary laboratory endpoint -- the cumulative number of new T2 lesions 4 years after randomization -- "when it was clear that the number of enrolled patients was lower than expected," the researchers wrote.
Overall, Mancardi and colleagues found fewer T2 lesions in the stem-cell group than in the mitoxantrone group during follow-up at a median of 2.5 lesions versus a median of eight lesions.
This effect was evident in the first year and was sustained through four years of follow-up, they reported. It was also maintained in all sensitivity analyses. It also resulted in complete suppression of active inflammatory lesions as measured by gadolinium-enhancing lesions, with no stem-cell patients having new lesions compared with 56 per cent of those on mitoxantrone.
The annualized relapse rate was also lower for stem-cell patients. However, there was no significant difference in terms of progression of disability between groups, occurring in 48 per cent of the mitoxantrone group and 57 per cent of the stem-cell group, with no differences in EDSS changes at any point, the researchers said.
Mancardi and colleagues attributed this to the study being underpowered to look for this outcome.
In addition to this limitation, and the fact that the study was changed from phase III to phase II, it was also limited by its small number of cases and by a lack of data on quality of life and brain atrophy outcomes.
In an accompanying editorial, Paolo Muraro, MD, PhD, of Imperial College London, agreed that the lack of improvement in progression of disability was likely due to the study being underpowered.
Muraro also noted that mitoxantrone might not be the contemporary choice of comparator "having lost traction because of its cardiac toxicity and risk of lymphoma," although it was the most appropriate control treatment at the time the trial was started.
Given that stem-cell transplant isn't a licensed therapy for MS, more work is needed, Muraro said, noting that a phase III trial currently underway is likely to gain traction because the current study will "raise interest and catalyse activities to move forward with the new trial."
The study was supported by the Italian Multiple Sclerosis Foundation.
Mancardi disclosed relevant relationships with Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi, and Teva. Many co-authors disclosed multiple relevant relationships with industry including Biogen Idec, Novartis, Merk-Serono, Genzyme, Teva Pharmaceutical Industries, Genmab A/S, and Bayer Schering Pharma.
Muraro disclosed no relevant relationships with industry.
Source: MedPage Today © 2015 MedPage Today, LLC (12/02/15)
Alkermes plc has reported positive top-line data from a phase I study on its experimental MS drug, ALKS 8700. ALKS 8700 is a novel monomethyl fumarate (MMF) molecule being developed for the treatment of MS.
The three-part, randomized, double-blind phase I study was conducted to evaluate the safety, tolerability and pharmacokinetics (PK) of several oral formulations of ALKS 8700 as compared to both placebo and active control groups in 104 healthy volunteers.
Data from the phase 1 study revealed that ALKS 8700 provided MMF exposures with less variability and improved gastrointestinal (GI) tolerability when compared to Tecfidera. Patients reported lower GI-related adverse events when treated with ALKS 8700 (8.3 per cent) as compared to Tecfidera (41.7 per cent). Moreover, the candidate was also found to be well tolerated during the course of the study.
Encouraged by the positive results from the phase I study, Alkermes plans to conduct a meeting with the FDA and move a twice-daily dose of ALKS 8700 into a pivotal development program this year.
Source: Zacks Copyright © 2015 Zacks Investment Research (11/02/15)
Switching multiple sclerosis patients with disease activity despite treatment with a first-line injectable to oral fingolimod (Gilenya) was associated with fewer relapses than switching them to another standard injectable, researchers have found.
In a study, patients on either interferons or glatiramer acetate (Copaxone) who were switched to fingolimod had a significantly lower mean annualized relapse rate than those who changed to another injectable immunomodulator, according to Tomas Kalincik, MD, PhD, of Royal Melbourne Hospital in Australia, and colleagues.
Patients in the study, reported online in JAMA Neurology, were switching medications following clinical relapse or disability progression while on the initial treatment.
In an accompanying editorial, Olaf Stuve, MD, PhD, of the University of Texas, and Diego Centonze, MD, PhD, of To Vergata University and Hospital in Rome, said the study adds to growing evidence that switching to newer agents like natalizumab (Tysabri) or fingolimod may be more effective.
Although it was an observational study, it assessed high-quality data and used appropriate propensity score matching to control for potential confounding factors, they wrote.
They noted, however, that the study's median follow-up of 13.1 months may be "too short to draw definite conclusions on the relapse rate."
Kalincik and colleagues conducted their matched retrospective analysis of data that was collected prospectively from MSBase, which collects data on MS patients in routine clinical care, from July 1996 to April 2014.
Patients with relapsing-remitting MS had been on a beta-interferon drug or glatiramer acetate for at least 6 months before making the change to another injectable (beta-interferon or glatiramer acetate) or to fingolimod because of clinical disease activity. They were then observed on the new medication for at least 3 months. Some of the patients initially taking a beta-interferon drug were switched to a different beta-interferon.
Overall, 379 patients in the injectable group were matched to 148 patients in the fingolimod group. Median follow-up was 13.1 months.
Kalincik and colleagues found that those switched to fingolimod not only had a lower mean annualized relapse rate but also a lower risk of first on-treatment relapse than those switched to another injectable immunomodulator.
Those changed to the oral drug also had a lower risk of disability progression and a higher rate of disability regression (HR 2.0, 95% CI 1.2-3.3, P=0.005), they reported.
They also had a lower rate of treatment discontinuation at 2 years.
The researchers noted that sensitivity analyses replicated in full the relapse and disability outcomes seen in the primary analysis. They did not, however, replicate the finding that switching to fingolimod improved treatment persistence, suggesting that this finding be interpreted with caution.
Kalincik and colleagues concluded that in the absence of randomized clinical trials, use of high-quality observational data provides an important tool for comparisons of drug effectiveness in a real-world setting.
In their editorial, Stuve and Centonze agreed that the quality of observational data in their study can provide "crucial information to support decision making relevant for MS management in real-world practice."
They said the results provide the first evidence that "switching to fingolimod is superior to switching to a second injectable immunomodulator with respect to disability outcomes, likely owing to the more efficient prevention of relapses associated with an incomplete recovery."
The results are in line with studies such as TRANSFORMS, one of the clinical trials leading up to fingolimod's approval, which found patients with active disease activity despite immunomodulatory therapy "may still have optimal disease control after switching to fingolimod."
In addition to the limitation of a short follow-up time, the study was also limited by lack of data on interferon-neutralizing antibodies, and because patients who were switched from one interferon preparation to another may not have served as true controls: "Most MS experts would not likely recommend this strategy because the agents are biochemically almost identical, and their mechanisms of action identical," they noted. The study, which was funded by fingolimod's manufacturer, also did not examine switches to natalizumab or newer oral agents.
Still, they concluded that evidence has accumulated that "escalating to the more effective medications natalizumab or fingolimod should be an early consideration for most patients with breakthrough disease. Switching to another injectable immunomodulator may still be considered in certain cases only."
The study was supported by Novartis, MSBase Foundation, Multiple Sclerosis Research Australia, National Health and Medical Research Council, and the Center for Research Excellence.
MSBase Foundation receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi.
The researchers disclosed financial relationships with Biogen Idec, Novartis, Genzyme, Merck Serono, Teva, Bayer Schering, Sanofi, Lundbeck, Bayer, Biologix, GSK, Roche, and bioCSL.
The editorialists disclosed financial relationships with Teva, Opexa, Merck Serono, Genzyme, Bayer Schering, Biogen Idec, Novartis, Almirall, GW Pharmaceuticals, Roche, and Mitsubishi.
Source: MedPage Today © 2015 MedPage Today, LLC (11/02/15)
In a paper published in the journal Lancet Neurology, an international team of researchers from Edinburgh, Cleveland and Vienna, under the leadership of Hans Lassmann, Head of the Department of Neuroimmunology at the MedUni Vienna, has for the first time documented the pathological progress of multiple sclerosis from its early to late stage and also shown that inflammatory and neurodegenerative processes have a role to play.
Until now, there have been two approaches to categorising the condition: the first approach regards MS as a disease of the nervous system that is inflammatory throughout, with the inflammation also being responsible for the subsequent neurodegenerative damage. The second approach postulates that the condition ultimately progresses from an inflammatory condition into a neurodegenerative one. In their current paper however, the team of researchers has demonstrated that MS is comprised of both factors - and that the inflammatory process acts as a "driving force" from the onset right to the end, and that neurodegenerative processes also occur in the so-called progressive, late phase that damage the brain.
Lassmann said: "The inflammatory process, which can be treated effectively in the early stages, becomes less pronounced with age. However the neurodegenerative damage increases. This also explains why drugs that initially work well later lose their effectiveness."
In the later stages of the condition, "amplification mechanisms" are triggered: the damage becomes amplified - and in a "self-contained" cycle that continues to cause destruction. The neurodegenerative damage in the brain activates microglial cells that also drive the disease forward, along with the formation of oxygen radicals that destroy lipids and proteins in the brain. At the same time, damage occurs to the mitochondria, which act as the power plants and energy providers to cells in the brain. This - coupled with normal brain ageing and the associated deposition of iron - also causes further damage.
New approaches to treatment could be developed based on the new discoveries about all of these mechanisms, say the researchers. "There are two routes", says Lassmann. "First, drugs could be developed that have an anti-inflammatory effect in the brain too, not just suppressing the defence response in the blood and lymphatic organs. Secondly, neuroprotective treatments could be developed that block the amplification mechanisms and damage to the mitochondria, thereby preventing consequential damage."
Clinical studies involving a number of potentially useful medications are already under way on the basis of this new data. The results will not be known for at least five years.
Lassmann said: "I firmly believe that in the foreseeable future, so within the next five to ten years, we will be successful in fighting the amplification mechanisms and slowing down the progressive phase further."
Source: Health Canal (11/02/15)
A new drug for the treatment of multiple sclerosis is being trialled in Australia.
The potential new treatment is derived from the same bacteria that causes acne in teenagers and aims to stimulate responses in the immune system. Principal investigator Dr Bob Soh, from the Nucleus Network in Melbourne, said there are currently no effective treatments for secondary progressive MS. Already eight people in Victoria are signed up to the phase 2B trial of the drug MIS416, reports the Herald Sun, which will determine if the drug can improve their symptoms.
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.
Trial participants are given weekly infusions of the drug or a placebo.
Dr Soh said that at the end of a 52-week trial period scientists would “unblind the trial” giving those who received the placebo the option of receiving the medication.
Trials of the drug in New Zealand have shown modest improvements in symptoms.
Stephen Mudgway, 51, has been on the drug for three years. He said: “Before I was on the drug I was sleeping for 18 hours a day, but it has given me my life back.”
In addition to the reduction in fatigue, the father of three has noticed improvements in his hand/eye coordination, cognition and he can stand for longer periods of time.
Results of the trial, which has also just been opened to Queenslanders, are expected to be known within two years.
Nucleus Network is one of Australia’s leading clinical research organisations for the conduct of early-phase clinical trials for the development of new medicines.
Source: Herald Sun Copyright News Corp 2015 (09/02/15)
Vision impairments due to multiple sclerosis is common but an under studied area, according to a report published in Brain. Researchers from both the United States and the United Kingdom reported on an international meeting of investigators aiming to develop and study visual outcomes in MS. The Dublin meeting was attended by more than 60 investigators in the realms of MS, neuro ophthalmology, clinical trial design, and evaluation of clinical outcome measures from Europe, North America, Asia, and Australia.
First, the researchers examined optic neuritis associated with MS, which is common among patients. The symptoms are described as several days of visual loss and, often, peri orbital pain exacerbated by eye movements. Complete vision loss is uncommon, however. Improvement of vision takes place typically after about 1 month following symptom onset. About 95 percent of patients achieve 20/40 high contrast visual acuity (HCVA), although many patients experience decreases in vision related quality of life (QOL) after five to eight years. There are short term treatments, typically intravenous methylprednisolone, which can speed recovery, but nothing offers long term benefits. Optical coherence tomography (OCT) offers a good option, the researchers believe, in studying therapies for neuroprotection and repair in MS.
The attendees also believed that patient reported outcomes are equally, if not more, important than clinical outcomes in measures of visual function, structure, and electrophysiology in their relation to patient QOL.
“Ideally, visual measures used in MS clinical trials should be standardized, reliable, practical, tolerated by study participants, and applicable for both adult and pediatric populations,” the authors wrote. “Aspects include visual function, vision specific QOL, structural markers, and electrophysiological tools.”
More comprehensive studies of visual dysfunction as secondary outcomes in clinical trials are needed, and particularly for progressive MS, the attendees determined. But more trials which aim to improve visual outcomes following optic neuritis are needed, as well.
“It is imperative that trials focusing on acute optic neuritis have sufficiently stringent eligibility criteria to insure accurate diagnosis and to avoid enrolling participants with other forms of optic neuropathy or causes of visual loss,” the authors concluded. This is especially true in pediatric MS cases, although they are rare, which present many study challenges for researchers, the authors reported.
“The capacity for measures of visual function, QOL, visual pathway structure, and electrophysiology to show not only deterioration but also improvement will be critical in the emerging era of agents that repair and protect the nervous system,” the authors said. “Vision research in MS will continue to require and benefit from the collaborative approach that has contributed to its success over the past decade.”
Source: HCP Live © HCP Live 2015 (09/02/15)
Drug development company Rock Creek Pharmaceuticals has announced a new clinical trial application with the Medicines Healthcare Products Regulatory Agency (MHRA) has been approved. The company is set to proceed with a Phase I study of Anatabine Citrate, a chemical that is found naturally in aubergine, potatoes, green tomatoes and other members of the Solanaceae family of plants, as well as in tobacco and tobacco smoke. The chemical is known for its anti-inflammatory properties unique from other anti-inflammatory drugs on the market, and may benefit patients with multiple sclerosis (MS).
The Phase I study will evaluate Anatabine’s pharmacokinetic profile in the form of modified release formulation prototypes, and its safety and tolerability profiles in healthy volunteers. The first two parts will involve an open-label, non-controlled, single-dose study on 14 healthy participants, using six formula variations, with each administered dose spaced 7-14 days apart. The variations will be distinct in dose and duration of therapeutic action. This will allow the company to determine which formulation is most ideal, based on safety. The third and last part of the Phase I study will be a double-blind, placebo-controlled, seven-day multiple dose study of the identified optimal formulation in healthy subjects.
“We are delighted to have been granted regulatory approval to begin our Phase I studies in the UK. This is the first clinical phase for our lead drug and will focus on safety and tolerability of six different formulations, five of which have modified release profiles and are of different doses. We look forward to generating our first human clinical data under this CTA,” said Rock Creek Pharmaceuticals CEO Dr Michael Mullan.
Rock Creek’s UK-based partner, Quotient Clinical, is set to begin enrollment of healthy subjects this month. While the company expects the study to stretch well into August, they expect to have a significant amount of research findings by mid-2015. Rock Creek also announced Quotient Clinical will be utilizing its RapidFACT® (Rapid Formulation development And Clinical Testing) service to hasten the development of these novel, oral, modified release formulations that have been co-developed between the two companies.
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (03/02/15)
Study looks at glucose and MS(03/02/15)
A study by researchers from Finland and Colorado have found that there may be a link between how the body deals with glucose and mobility in people with MS.
Eight patients with MS and eight controls performed 15 minutes of treadmill walking at a self-selected pace, during which the glucose analogue [18F]-Fluorodeoxyglucose (FDG) was injected. Immediately after the period of walking, the participants underwent a positron emission tomography (PET) scan.
Patients with MS had lower FDG uptake in 40 per cent of the brain compared to the healthy controls and walked at a slower speed. Within the area of lower FDG uptake 15 regions were identified. Of these, 13 were found to have strong to moderate correlations to walking speed within the healthy controls. Within patients with MS, only three of the 15 regions showed significant correlations.
The researchers concluded that walking impairments in patients with MS may be due to network-wide alterations in glucose metabolism. |It is hoped that understanding how brain activity and metabolism are altered in patients with MS will allow for better measures of disability and status of the condition.
Source: Frontiers © 2007 - 2015 Frontiers Media S.A. (03/02/15)
Acorda Therapeutics has today announced safety and tolerability data from a Phase 1 clinical trial of rHIgM22, a remyelinating antibody being studied for the treatment of multiple sclerosis. The trial, which followed participants for up to six months after receiving a single dose of rHIgM22, found no dose-limiting toxicities at any of the five dose levels studied. Based on this, the Company intends to advance clinical development of rHIgM22.
“We’re encouraged by the outcome of this trial, which showed that rHIgM22 was well-tolerated at all of the dose levels we studied,” said Anthony Caggiano, M.D., Ph.D., Acorda’s Senior Vice President of Research and Development. “We are currently developing the protocol for our next Phase 1 clinical trial of rHIgM22. The data from this study will help inform the design of the next trial, which will enroll people with MS who are experiencing an active relapse.”
This was a multi-center, double-blind, randomized, placebo-controlled study designed to evaluate safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of rHIgM22 in participants with any type of MS who were clinically stable for at least three months. All participants remained on their existing MS treatment regimens, including disease-modifying therapies.
The first part of the study included five cohorts, with each cohort receiving a higher dose of rHIgM22 than the previous one. Each cohort consisted of 10 participants (eight receiving drug, two receiving placebo), who were followed for three months after receiving a single dose of study medication. In the second part of the study, 21 participants were randomized to receive placebo or one of the two highest doses of rHIgM22 from the first part of the study. These participants were followed for six months to assess safety and tolerability. The second part of the study also included several exploratory clinical, imaging and biomarker measures, which are still being analysed. The study was not powered to determine statistical significance on these measures.
Additional details from the trial will be presented at future medical meetings.
Across all of the study groups, 55 participants received one of the five doses of rHIgM22 and 17 received placebo (no sample size power calculation was used to determine the number of participants in each group). There were no dose-limiting toxicities and no serious adverse events (SAE) in any of the five rHIgM22 dose levels in the study. There was one SAE of squamous cell carcinoma in a placebo-treated participant.
The most commonly observed adverse events (>5 per cent in the combined rHIgM22 treatment groups) reported in the study were: headache, contact dermatitis, MS relapse, infusion site hematoma, fatigue, arthralgia, back pain, muscular weakness, neck pain, pain in an extremity, pruritus, contusion, and flushing. No participants withdrew due to adverse events.
No safety signals were identified by standard clinical MRI evaluations, or standard clinical, laboratory or ECG assessments.
rHIgM22 is a recombinant human monoclonal antibody identified in the laboratory of Moses Rodriguez, M.D. at Mayo Clinic. In preclinical studies, rHIgM22 has been found to protect oligodendrocytes and stimulate them to repair areas of demyelination. rHIgM22 treatment also resulted in sustained improvements in motor activity in preclinical models.
Source: Finances © 2015 Finances International Ltd. (02/02/15)
Australia gets cutting-edge microscope(02/02/15)
The "secrets of life" could be revealed by a powerful new microscope, the only one of its kind in Australia.
THE $5million, three-metre tall microscope, unveiled at Monash University in Melbourne, allows researchers to see molecular structures at very high resolution.
"This is one of the most exciting days of my life," said Professor James Whisstock, the Australian Research Centre's director of advanced molecular imaging.
Professor Whisstock hopes the microscope will lead to better treatments for cancer, diabetes and multiple sclerosis.
"Understanding our immune system is central to fighting cancer, infectious diseases such as malaria, and auto-immune diseases such as diabetes, rheumatism and multiple sclerosis.
"The key to understanding and treating these diseases lies in understanding how proteins and cells interact at the molecular level."
Professor Whisstock said the instrument highlights how physics and engineering together can be used to answer biological problems.
"We need physicists and engineers to be able to build these devices that can see the secrets of life."
Until now Australian scientists had to travel to Europe, the UK or the US in order to access similar microscopes.
"The problem with that is transporting biological material internationally is quite hard."
The Dutch-made Titan Krios instrument works by firing electrons through a sample.
Some of the electrons in the beam are deflected and these rays can be used to create a 2D image of the sample. Multiple 2D images can then be automatically pieced together to create 3D images of molecules.
Source: The Australian (02/02/15)