MS news and research
This page documents breaking multiple sclerosis news and research stories as they occur during the month.
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America’s National Multiple Sclerosis Society has provided a grant to a Wayne State University School of Medicine professor to explore a new model of MS pathology.
Alexander Gow, Ph.D., the Charles H. Gershenson Distinguished Fellow Professor and associate director of the WSU Centre for Molecular Medicine and Genetics, will use the three-year, $663,959 grant for his study Neurodegeneration Associated With Metabolic Stress In Oligodendrocytes.
From the early-mid phases of MS, Dr Gow said, the clinical symptoms are caused by damage to the brain in the forms of autoimmune lesions, atrophy in the white matter and grey matter of the brain and cognitive deficits. So far most studies have focused on finding disease-modifying therapies for the autoimmune component of MS, but have tended to ignore the cognitive changes.
Several important findings have come to light in recent years, he said, including the revelation that strong immunosuppression of patients for several years only modestly slows MS progression while damage to cortical brain regions continues.
“In this study, we tackle both of these issues using a new model of MS pathology that does not involve autoimmune stimulation to generate disease symptoms,” said Dr Gow, who also is a professor of Paediatrics and of Neurology for WSU. “Rather, we activate metabolic stress in oligodendrocytes to cause dysfunction and death of these cells, which is a potential disease mechanism that has gained experimental support from several laboratories.”
Oligodendrocytes are a type of cell that produce a membrane called myelin that coats axons, the pathways by which the brain sends messages to the muscles.
Dr Gow will seek to determine whether this nonimmune-mediated animal model can recapitulate MS pathology and whether he can find evidence for behavioural changes and cognitive decline. He also will test a drug treatment designed to protect oligodendrocytes and neurons from the degenerative changes associated with inducing primary metabolic stress.
There is increasing evidence, Dr Gow said, to indicate autoimmune attacks on the central nervous system may be a secondary event rather than the primary cause of MS. This indicates researchers must cast a broader net to test new ideas and develop alternative models that could shed fresh light on MS aetiology.
Source: Newswise ©2015 Newswise, Inc (02/07/15)
Tags: MS, multiple sclerosis, Wayne State University, Neurodegeneration, oligodendrocytes, autoimmune, myelin, research
Genentech has announced positive results from two studies evaluating ocrelizumab for people with relapsing multiple sclerosis (MS).
The studies (called OPERA I and OPERA II) met their primary and major secondary endpoints.
Treatment with ocrelizumab significantly reduced the annualised relapse rate (ARR) over a two-year period compared with interferon beta-1a. Ocrelizumab also significantly reduced the progression of clinical disability compared with interferon beta-1a, as measured by the Expanded Disability Status Scale (EDSS).
Treatment with ocrelizumab also led to a significant reduction in the number of lesions in the brain compared with interferon beta-1a, as measured by MRI, say researchers.
The number of recorded “adverse events”, or side effects, associated with ocrelizumab was similar to interferon beta-1a in both studies, the most common of which were mild-to-moderate infusion-related reactions. The incidence of serious adverse events associated with ocrelizumab, including serious infections, was also similar to interferon beta-1a.
Sandra Horning, MD, chief medical officer and head of Global Product Development, said: “Ocrelizumab has the potential to make a meaningful difference for people with MS. Based on these compelling results, we plan to submit the data for review to U.S. and EU regulatory authorities in the first quarter of 2016.”
Further analyses of the OPERA studies are ongoing and results from a Phase III study of ocrelizumab in people with primary progressive MS (PPMS) are expected later this year.
Source: Business Wire ©2015 Business Wire (30/06/15)
Tags: ms, multiple sclerosis, primary progressive multiple sclerosis, relapsing multiple sclerosis, ocrelizumab, Rebif, interferon beta-1a
A new study published in the Journal of Neurology, Neurosurgery and Psychiatry has found long-term Gilenya therapy can maintain a low disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). The study, Long-Term (up to 4.5 years) Treatment With Fingolimod (Gilenya) In Multiple Sclerosis: Results From The Extension Of The Randomised TRANSFORMS Study, was conducted by an international team of researchers.
Gilenya is an immunomodulating drug and an effective therapy for RRMS. The safety, tolerability and efficacy of two oral doses (0.5 or 1.25 mg once daily) were assessed in the 12-month, randomised, double-blind phase three clinical trial called TRANSFORMS (NCT00340834) in relapsing remitting MS (RRMS) patients in comparison to treatment with interferon (IFN) beta-1a. The study revealed Gilenya at both doses significantly improved clinical and magnetic resonance imaging (MRI) outcomes with patients experiencing a reduction in the frequency of relapses in comparison to IFN beta-1a treatment.
Researchers conducted an extension study (up to 4.5 years) of the TRANSFORMS trial in which RRMS patients previously receiving Gilenya continued the same treatment and those under IFN beta-1a therapy received either 0.5 or 1.25 mg of the drug. The team analysed the patient’s annualised relapse rate, disability progression and MRI measures. In total, 1027 RRMS patients entered this extension study and only 772 completed it.
Researchers found the annualised relapse rate was significantly lower in patients under continuous Gilenya treatment than in patients who switched over from IFN beta-1a. Nevertheless, patients who switched from IFN to Gilenya exhibited a 50 per cent reduction in annualised relapse rate and a reduced MRI disease activity. Among the patients who switched therapies, there was an increase of around 50 per cent in the proportion of patients with no evidence of disease activity in the first year after Gilenya treatment. After 4.5 years of Gilenya therapy, both disability progression and MRI outcomes were not significantly different between the groups.
The research team concluded that switching from IFN beta-1a to Gilenya improved treatment efficacy, and that Gilenya therapy has a continuous long-term effect in maintaining a low disease activity in RRMS patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (30/06/15)
Tags: ms, multiple sclerosis, Gilenya, relapsing-remitting multiple sclerosis, RRMS, IFN beta-1a, research
Researchers at Immco Diagnostics and the State University of New York have reported in the journal PLoS One that the frequency of specific auto reactive antibodies does not differ between patients with multiple sclerosis (MS) and people without the condition — a finding that could lead to improvements in diagnosis. The study is entitled “Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis.”
Patients with the progressive form of MS usually have a poor response to treatment, say researchers, as all approved therapies are currently indicated for the relapsing-remitting form. The progressive forms can be either primary progressive MS, where patients develop this form from the time of diagnosis, or secondary progressive MS, where patients initially experience a relapsing-remitting phase of neurological dysfunction that later evolves into a secondary progressive disease.
Immune auto reactive B cells and their antibody response have been reported previously by researchers to play a key role in MS development. In this study, the goal was to assess auto reactive antibodies’ frequency in patients with different MS forms, and see if they match up with clinical and magnetic resonance imaging (MRI) measures of MS disease progression. Possible co-morbidities were also evaluated, including infection by the Epstein-Barr virus (EBV), a common human herpes virus that targets B cells and which has been linked to an increased risk of MS.
Researchers analysed serum samples from patients and healthy controls for autoantibodies against three known antigens related to MS [CSF114(Glc), KIR4.1a and KIR4.1b] and against 26 different antigens linked to other autoimmune disorders, including systemic sclerosis, lupus, rheumatoid arthritis, among others.
Researchers found the frequencies of auto reactive antibodies against CSF114(Glc), KIR4.1a and KIRK4.1b were similar between healthy controls and RRMS, PPMS and SPMS patients, suggesting that these antibodies are not associated with MS or disease progression. In fact, none of the several autoreactive antibodies analysed, including anti-EBV antibodies, were found to differ in terms of frequency between MS patients and healthy controls.
The research team concluded that the frequency of the autoantibodies analysed in MS patients is similar to the ones in healthy controls, and that the presence of autoreactive antibodies was not associated with clinical and MRI measures of MS disease progression. Researchers expressed their concern that CSF114 and anti-KIR 4.1a and KIR 4.1b peptide antibodies might not have the diagnostic MS properties that were previously thought to have. These new insights could help physicians improve the diagnosis of MS in the future — a key advancement, since diagnosing and treating MS as early as possible is critically important to mitigating the disease.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (26/06/15)
Tags: MS, multiplesclerosis, autoantibodies, F114(GLC), KIR4.1A KIR4.1B, Research
New MS guidelines released(25/06/15)
The Association of British Neurologists (ABN) has published new guidelines for how Disease Modifying Therapies (DMTs) for relapsing remitting multiple sclerosis should be monitored and prescribed in the UK, emphasising the “right treatment at the right time.”
There are currently ten DMTs available on the NHS and eleven in Scotland. For MS patients, being prescribed a DMT can positively impact the course of multiple sclerosis and the prevention of relapses, as well as slow down disease progression. In short, the ABN contends the therapies enable individuals living with multiple sclerosis to have a much greater control of their condition and consequently their lives.
The new guidelines suggest treatment with DMTs should begin as soon as possible after diagnosis. Additionally, MRI scanning should also be used as a routine tool to support diagnosis, to assess prognosis and to offer additional insight into treatment decisions and their possible impact. The ABN also stresses that every decision about appropriate treatment options, including the prescription of DMTs, should be made jointly between the patient and their neurologist.
Nick Rijke, Executive Director of Policy and Research at the MS Society, said: “We are very pleased the ABN recommends treatment with DMTs and recognises the importance of shared decision-making between neurologist and patient when deciding which route to take. We also welcome the emphasis on MRI scanning to support diagnosis and make better treatment decisions. The combination of these recommendations should help ensure fast diagnosis and appropriate, timely treatment for people with MS. There are ten DMTs available on the NHS in the UK (11 in Scotland). However our evidence from 2012 showed six in ten people with relapsing-remitting MS are not taking DMTs. We call on government bodies like NICE and NHS England to ensure that everyone with MS has access to the right treatment at the right time no matter where they live.”
At present, there are few therapeutic options for those with progressive forms of multiple sclerosis, and those who have the relapsing-remitting form of the disease (RRMS) are at risk of eventually having their MS develop into secondary progressive multiple sclerosis (SPMS). Since some approved DMTs are believed to slow the progression of MS, experts stress that their use is vital to delaying RRMS patients’ decline into SPMS.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (25/06/15)
Tags: MS, multiple sclerosis, Disease Modifying Therapies, relapses, progression, relapsing-remitting, RRMS
Medical marijuana may be useful in treating chronic pain and spasticity but less effective for other conditions, according to the results of a review published in the Journal of the American Medical Association.
The researchers singled out 79 clinical trials for inclusion in their analysis. The studies tested the effects either of medical marijuana itself or drugs that contain plant-derived or synthetic compounds found in marijuana, including studies of dronabinol, a U.S. Food and Drug Administration-approved medication that contains synthetic tetrahydrocannabinol. The authors said that they found and included only two studies that evaluated medical marijuana itself, rather than a derivative medication.
The review revealed moderate-quality evidence to support medical marijuana use in treating chronic pain. The evidence also showed that the medications could help multiple sclerosis patients who suffer from spasticity. The researchers found low-quality evidence for the drugs' use in treating sleep disorders; nausea or vomiting related to chemotherapy; for producing weight gain in people with HIV; or for reducing symptoms of Tourette syndrome.
"There is evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity," lead author Penny Whiting, PhD, a senior research fellow at the University of Bristol told HealthDay.
"However, this needs to be balanced against an increased risk of side effects such as dizziness, dry mouth, nausea, sleepiness, and euphoria."
Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (25/06/15)
Tags: MS, multiple sclerosis, cannabis, Medical marijuana, chronic pain, spasticity, research
Pain in multiple sclerosis (MS) patients is independently predicted by anxiety, according to a study published in Pain Medicine.
Jelena Drulovic, MD, PhD, from the Clinical Centre of Serbia in Belgrade, and colleagues conducted an international, cross-sectional survey to examine the prevalence, intensity, and associations of pain in MS. A total of 650 consecutive patients, diagnosed according to the Revised McDonald Diagnostic Criteria, were recruited from seven MS centres. During face-to-face interviews with neurologists, a semi-structured questionnaire was administered.
The researchers found the lifetime prevalence of pain was 66.5 per cent (point prevalence, 44.3 per cent). Comorbidity of pain and depression exhibited a prevalence of 29.1 per cent. There were significant associations between pain and older age, primary-progressive MS, higher Expanded Disability Status Scale score, and higher scores of Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. Anxiety was found to be an independent predictor of pain in multivariate linear regression analysis.
"We confirmed high prevalence of pain, affecting approximately more than half of patients during the course of MS," the authors wrote.
"Pain in MS is associated with disability, depression, and especially with anxiety, which has significant implications for treatment."
Reference: Drulovic J et al. Pain Medicine. 2015; doi:10.1111/pme.12731.
Source: Neurology Advisor Copyright © 2015 Haymarket Media, Inc (25/06/15)
Tags: MS, multiplesclerosis, pain, anxiety, Expanded Disability Status Scale, research
The early diagnosis of certain types of cancer, multiple sclerosis and neuromyelitis optica, may soon be facilitated by the use of a nanometric sensor capable of identifying key biomarkers.
The nanobiosensor was developed at the Federal University of São Carlos (UFSCar), Sorocaba, in partnership with the São Paulo Federal Institute of Education, Science & Technology (IFSP), Itapetininga, São Paulo State, Brazil and was originally designed to detect herbicides, heavy metals and other pollutants.
"It's a highly sensitive device, which we developed in collaboration with Alberto Luís Dario Moreau, a professor at IFSP," said physicist Fábio de Lima Leite, a professor at UFSCar and the coordinator of the research group.
"We were able to increase sensitivity dramatically by going down to the nanometric scale,"
The nanobiosensor consists of a silicon nitride (Si3N4) or silicon (Si) nanoprobe with a molecular-scale elastic constant and a nanotip coupled to an enzyme, protein or other molecule.
When this molecule touches a target of interest, such as an antibody or antigen, the probe bends as the two molecules adhere. The deflection is detected and measured by the device, enabling scientists to identify the target.
"We started by detecting herbicides and heavy metals. Now we're testing the device for use in detecting target molecules typical of nervous system diseases, in partnership with colleagues at leading centres of research on demyelinating diseases of the central nervous system"
The migration from herbicide detection to antibody detection was motivated mainly by the difficulty of diagnosing demyelinating diseases, cancer and other chronic conditions before they have advanced beyond an initial stage.
The criteria for establishing a diagnosis of multiple sclerosis or neuromyelitis optica are clinical (supplemented by MRI scans), and patients do not always present with a characteristic clinical picture. More precise diagnosis entails ruling out several other options first.
The development of nanodevices will be of assistance in identifying these diseases and reducing the chances of false diagnosis.
The procedure can be as simple as placing a drop of the patient's cerebrospinal fluid on a glass slide and observing its interaction with the nanobiosensor.
"If the interaction is low, we'll be able to rule out multiple sclerosis with great confidence," Leite said.
"High interaction will indicate that the person is very likely to have the disease." In this case, further testing would be required to exclude the possibility of a false positive.
"Different nervous system diseases have highly similar symptoms. Multiple sclerosis and neuromyelitis optica are just two examples. Even specialists experience difficulties or take a long time to diagnose them. Our technique would provide a differential diagnostic tool," Leite said.
The next step for the group is to research biomarkers for these diseases that have not been completely mapped, including antibodies and antigens, among others. The group has begun tests for the detection of head and neck cancer.
Source: Phys.org © Phys.org 2003 - 2015, Science X network (24/06/15)
Tags: MS, multiplesclerosis, cancer, nervous system diseases, nanometric, neuromyelitis optica, research
Eye doctors could soon be using computing power to help them see individual cells in the back of a patient's eye, thanks to imaging technology developed by engineers at the University of Illinois.
Such detailed pictures of the cells, blood vessels and nerves at the back of the eye could enable earlier diagnosis and better treatment for degenerative eye and neurological conditions.
The technique applies adaptive optics – the method astronomers use to correct telescope images so they can more clearly see stars beyond the twinkling – to the instruments that scan the retina at the back of the eye. However, the Illinois team does the correction computationally, instead of using complex hardware. Led by electrical and computer engineering professor Stephen Boppart, the research team published its work in the journal Nature Photonics.
"The eye has always been a bit of a challenge to image. It's a very complicated organ," said Dr Boppart.
"There are many microscopic structures that are hard to see. Many diseases that affect vision also start at the microscopic level, so being able to see those early changes is going to lead to better, earlier treatment."
The prevailing imaging technique in ophthalmology, known as optical coherence tomography or OCT, is useful for general imaging of the eye but cannot focus down to the scale of individual rods and cones, the light-sensitive cells lining the retina that make sight possible. In addition, OCT images are often blurred by the eye's imperfections and constant motion.
Computational adaptive optics applies complex algorithms to OCT data correcting for eye aberrations and motion, yielding high-resolution, real-time images that show individual cells and nerves.
Hardware-based adaptive optics systems have been developed to enhance OCT imaging with elaborate setups of lenses, mirrors and lasers, but such systems are so costly and unwieldy that they are impractical for clinical use, Boppart said. However, the new computational approach could be applied to existing OCT systems, with minor hardware updates to older systems for compatibility.
Computational adaptive optics also hold an advantage over hardware setups in that they can tailor themselves to a patient's unique eye structures and shape, and doctors can take one quick scan and afterward focus in on different parts of the eye.
"I think computational adaptive optics can be really helpful to the clinical community," said Fredrick South, a graduate student and a co-author of the paper.
"It could give ophthalmologists information that, currently, they have to infer from other measurements. They can't directly look at the photoreceptors and watch them die off during macular degeneration, for example. They just have to guess what's going on. It could be possible to use computational adaptive optics in these real-world applications both for diagnosis of disease and tracking of treatments."
The researchers are initially focusing on using computational adaptive optics to track age-related macular degeneration, a progressive eye disease, and multiple sclerosis. Since nerve fibres make up the top layer of the retina, the eye could be a unique window into nerve health for multiple sclerosis patients, Boppart said. The researchers hope the detailed pictures gleaned from applying computational adaptive optics can illuminate how changes in the retina correspond to disease severity and track how cells and nerves respond to treatments.
"The eye is so important, because we rely on sight more than any of our other senses," Boppart said. "Here's a technology that was developed basically to remove the twinkle from stars, and now we want to use it to correct imperfections left by Mother Nature, allowing us to see patients' eyes better and to help them more."
Source: Phys.org © Phys.org 2003 - 2015, Science X network (23/06/15)
Tags: MS, Multiple Sclerosis, degenerative eye, neurological diseases, research
Foundation forced to close over funding(23/06/15)
The Myelin Repair Foundation, founded and led by a multiple sclerosis patient Scott Johnson, will close at the end of August, it has been announced.
The decision by the Saratoga foundation comes at a time when drug developers are increasingly leaning on nonprofits to help them fund trials, find potential disease targets and attract patients to clinical trials.
But the MRF, with an average annual budget of about $5million, went beyond the old formula of partnering with industry players. It developed new ways to help researchers zero in on the degradation of myelin, licensing one mouse model in 2013 to biotech giant Biogen Inc. It funded academic research, but it also set up its own labs in Sunnyvale to accelerate discoveries.
The foundation's crowning achievement perhaps came in April, when it handed off development of a long-forgotten high blood pressure drug to the National Institutes of Health as a way to stop — and possibly repair — the damage caused by MS to the fatty myelin sheaths that typically protect nerve cells.
"Ironically even with tremendous success on the research side, we have struggled with raising enough money to keep up with our extraordinary low research costs," President Scott Johnson wrote in a letter to supporters.
Johnson founded the organisation in 2003, relying on donations from individuals and foundations from 29 countries to raise $55m over its life. But, Johnson noted, the National Multiple Sclerosis Society last year alone raised $250m.
A mere 56 donors provided 92 percent of the MRF's revenue, and, Johnson said, "several large donations" that MRF had counted on for the fiscal year that begins July 1 have not come through.
"Having to stop our efforts and close our doors is the worst case for all who devoted time and/or financial support to our endeavour to help all those impacted by MS," Johnson wrote. "Our consolation is that over the last eleven years we have had a dramatic impact on the myelin repair landscape."
Indeed, until a decade ago, most MS research focused on controlling inflammation caused by the immune system. MRF, instead, zeroed in on ways to stop the erosion of myelin and potentially restoring myelin in MS patients. The foundation's big push was to get a myelin-repair drug into clinical trials within a dozen years, and Johnson said he now believes that a neuroprotective or repair therapy will be available within 10 years.
One of the potential MS treatments with an MRF legacy could be guanabenz, or MRF-008. The drug was found by the University of Chicago's Dr Brian Popko, who has received MRF funding, to play an important role in the survival of oligodendrocytes in the presence of inflammation.
Working with the NIH, the Food and Drug Administration and other members of an MRF research consortium, the MRF helped to fund preclinical work on guanabenz, to find a manufacturer of the out-of-circulation drug and to line up a clinical trial protocol that could be used on a new generation of experimental MS drugs.
Guanabenz began an NIH-overseen trial in April, and the long battle to bring the drug into a trial was documented in a recent San Francisco Business Times story.
"What we have accomplished," Johnson said, "will live on through the people we have worked with and the discoveries we have made."
Source: San Francisco Business Times © BizJournals.com 2015 (23/06/15)
Tags: MS, Multiple Sclerosis, Pharmaceuticals, Myelin, Biotech, Funding, Scott Johnson, Myelin Repair Foundation
Researchers at the United Arab Emirates University in Abu Dhabi have published in the journal BMC Neuroscience new insights into the involvement of mitochondria and energy metabolism in the pathology of multiple sclerosis (MS) in rats.
The study is entitled Bioenergetics Of The Spinal Cord In Experimental Autoimmune Encephalitis Of Rats.
Mitochondria are small cellular organelles responsible for the production of energy (in the form of ATP) in the body through the process of respiration. Mitochondrial dysregulation has been linked to axonal damage and demyelination in MS human patients and the corresponding experimental autoimmune encephalomyelitis (EAE) model in mice.
Curiously, rodents have been reported to apparently recover from EAE with minimal neurological deficits. This recovery is thought to be linked to a downregulation of pro-inflammatory factors and clearance of infiltrating immune cells (T cells).
The cellular bioenergetics (energy metabolism) of the central nervous system (CNS) during the early development and clinical course of EAE has, however, been poorly investigated. In this study, the team hypothesized that the CNS bioenergetics may be used as a prognosis predictor of the disease and that it may explain disease remission in rodents, a recovery time where animals experience few or no symptoms. EAE susceptible and resistant rats were used and their oxygen consumption and ATP concentration in the spinal cord tissue were determined. Cell death (or apoptosis) was also assessed.
Researchers observed that in terms of cellular respiration in the CNS, no difference was found between diseased and healthy rats. Significant inflammation and apoptosis events were, however, observed in EAE susceptible animals, suggesting that both processes play a relevant role in the development of clinical disease, having little effect on mitochondrial function. These animals exhibited smaller mitochondria in the spinal cord regions with immune infiltrates. Demyelination events were also found in these specific regions at the initial stage of the disease.
The research team concluded that EAE at an early stage does not seem to significantly affect the CNS cellular respiration and ATP content, suggesting that the role played by mitochondria in demyelination and EAE development is minimal. The team hypothesizes that the recovery of rats with EAE might be due to the presence of a large population of functional mitochondria in regions of the spinal cord that have not been affected by the disease (no immune infiltrates). Based on the findings, the research team suggests that any intervention based on preserving the energy metabolism in EAE animals will likely improve disease outcome. Further studies are required to determine how these findings can be translated into the human context.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (23/06/15)
Tags: MS, Multiple Sclerosis, EAE, Energy Metabolism, Mitochondria, Research
Study suggests benefits of vitamin D(23/06/15)
A team of researchers from the Isfahan University of Medical Sciences in Iran, led by Dr Masoud Etemadifar, have conducted a randomised controlled clinical study in 15 pregnant women with low vitamin D levels and multiple sclerosis.
Women treated with 50,000 IU/week (International Units) of vitamin D3 showed significantly higher vitamin D levels and fewer symptoms related to MS six months after delivery of their babies, as measured by the expanded disability status scale.
Although not statistically significant, the relapse number among the study participants also appeared to be lower in women supplemented with vitamin D.
The study did have limitations in that it was only exploratory in nature and featured a small sample size.
However, the findings revealed that, compared to routine care, the supplementation of pregnant women with MS with standard high-dose supplementation of vitamin D had a significantly positive effect on the disease.
These results are promising and warrant the need for further studies with larger sample sizes and longer follow-ups to ascertain the true safety and efficacy of supplementation in this subgroup of patients.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (23/06/15)
Tags: MS, Multiple Sclerosis, Pregnancy, Vitamin D, Research
A company that specialises in turning University research into marketable drugs is licensing Harvard research related to the blue evergreen hydrangea root, a part of the plant that has been used in traditional Chinese medicine for centuries.
Allied-Bristol Life Sciences, a joint venture between university commercialisation specialist Allied Minds and US pharmaceuticals giant Bristol-Myers Squibb, is licensing research carried out by Professor Malcolm Whitman and Dr Tracy Keller at Harvard from 2002 onwards.
The pair found that the active ingredient in blue evergreen hydrangea root, called halofuginone, can block a type of rogue T-cell and also identified how it blocks these cells.
T-cells are the part of the immune system that tackles viruses, but rogue T-cells attack healthy cells and can cause inflammation and damage. This occurs in autoimmune conditions such as multiple sclerosis, type 1 diabetes and lupus.
Allied-Bristol Life Sciences is hoping to use the Harvard research, based on a synthetic form of halofuginone, to develop drugs to treat these types of conditions.
Whitman and Keller’s findings were published in 2012 and reported on the effects of halofuginone on a mouse with a model of multiple sclerosis. But this is the first time a company has explicitly stated they want to make a drug based on the research.
Blue hydrangea root has been used for at least 2,000 years in Chinese medicine and its efficacy was first noticed in the 1940s in the West, according to Harvard Magazine’s report of Whitman and Keller’s research.
But until the Harvard pair studied the root nobody knew exactly how it worked, meaning it was impossible to replicate its effects in a drug.
Allied-Bristol Life Sciences CEO Satish Jindal said: “The work done by Whitman and Keller is a terrific example of a promising early-stage therapeutic application that has the potential to make a significant difference to patients.
“We are pleased to support this project through the next phase of drug discovery to identify a candidate for clinical development. This is a great example of the type of university research that ABLS looks for, where our expertise and experience can accelerate bringing new therapies to patients that need them.”
Dr Whitman said: “Our research is at the right stage for an infusion of resources and expertise to accelerate its progression. We look forward to seeing the development of lead compounds from our laboratories into novel therapeutics for the treatment of fibrotic disease, and potentially other indications.”
Source: Business Insider Australia © 2007-2015 Allure Media (22/06/15)
More positive data reported by MedDay(19/06/15)
MedDay, a biotechnology company focused on the treatment of nervous system disorders is reporting additional positive data from its pivotal Phase III clinical trial, MS-SPI, with MD1003, a highly-concentrated pharmaceutical grade biotin, in patients with progressive multiple sclerosis.
The data shows an improvement of the Clinical Global Impression of change observed after 12 months of treatment with MD1003 and confirms the positive results presented at the American Academy of Neurology in April 2015.
Frederic Sedel, Chief Executive Officer of MedDay, said: "We are pleased to announce further positive findings which confirm the promising MD1003 Phase III data announced earlier this year. MD1003 remains the only drug to date that has demonstrated an ability to decrease the rate of disease progression and improve a significant proportion of patients with progressive MS.
"A second phase III placebo-controlled trial is underway looking at the effect of MD1003 in MS patients with permanent visual loss following optic neuritis and we look forward to announcing data from this trial later this year and potentially investigating a drug filing thereafter."
The Clinical Global Impression of change is a seven point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as:
One - very much improved;
Two - much improved;
three - minimally improved;
Four - no change;
Five - minimally worse;
Six - much worse;
Seven - very much worse.
During the MS-SPI trial, the Clinical Global Impression of change has been assessed by the clinician (clinician global impression, CGI) as well as by the patient (subject global impression, SGI) after 12 months of treatment. Mean CGI and SGI scores assessed at month 12 were statistically significantly better in the intervention group compared with the placebo group.
These results confirm the previously reported data of MS-SPI where the primary endpoint was defined as the proportion of patients who improved either on EDSS or on timed 25-foot walk (TW25) at M9, with a confirmation of the improvement at 12 months (M12) was met.
The mean change of EDSS between M0 and M12 decreased in the MD1003 group compared to progression in the placebo group. In the MD1003 arm, only four per cent of patients treated with MD1003 exhibited EDSS progression at M9 confirmed at M12 vs 13 per cent in the placebo group (p=0.07), which equates to a 67 per cent decreased risk of progression in the active arm within the studied period.
Source: Copyright PR Newswire © 2015 PR Newswire Association LLC (19/06/15)
Scientists at The Scripps Research Institute (TSRI) have teamed up with several other institutions and pharmaceutical companies, including the University of Southern California (USC), San Diego's Receptos Inc. and Japanese company Ono Pharmaceutical Co., Ltd., to publish the first 3D structures of a receptor implicated in many diseases of the brain and in normal physiology throughout the body.
Surprisingly, the structures revealed a new understanding of the body's use of cannabinoids—a naturally produced substance chemically related to marijuana.
The new research, published June 18, 2015, in the journal Cell, sheds light on the molecular architecture of receptors for a family of small fat molecules known as lysophosphatidic acid (LPA), part of a larger class of fat molecules (lysophospholipids) linked to conditions including hydrocephalus, pain, hypoxic brain damage, psychiatric disorders, multiple sclerosis, fibrosis and cancer.
"The study has particular relevance to understanding and possibly treating the brain," said TSRI Professor Jerold Chun. "This structure is the first for an LPA receptor—and it revealed a couple of surprises."
Chun is co-senior author of the study with Michael A. Hanson, president of GPCR Consortium and former director of structural biology at Receptos, and Raymond Stevens, director of the Bridge Institute at USC and founding director of iHuman Institute of ShanghaiTech University.
Chun and his colleagues first identified the protein, called lysophosphatidic acid receptor 1 (LPA1), in studies of the brain nearly 20 years ago. The LPA1 receptor sits within and spans membranes of cells to bind with LPA in the body. When bound, LPA1 sends a signal into the cell to influence a range of functions, such as cell migration, shape, survival and proliferation.
While the scientists knew the importance of LPA1, the Chun lab's studies into the biology of the molecule indicated that it was a kind of G protein-coupled receptor (GPCR), known to be difficult to image.
To overcome this challenge, in this study the team used techniques developed by Stevens and colleagues to stabilise the receptor in the presence of drug-like molecules synthesised by researchers at Ono Pharmaceutical. Stevens noted the work by Ono and the chemistry it did to enable the structural biology (with a focus on lung fibrosis) was a big breakthrough.
This collaboration enabled the formation of crystals that were used for x-ray crystallography, a high-resolution imaging technique.
The resulting data revealed two important features of LPA1.
One was the discovery that LPA1 lacks any sort of "cap" on top of it. Instead, it has an opening where ligands (binding partners, rather like keys to locks) can slip from the outside of the cell into the binding pocket. This allows ligands from aqueous sources to avoid the water-repelling lipids surrounding the receptor, solving the long-standing mystery of how LPA bound to proteins in blood and other fluids could easily activate LPA1.
Importantly, the researchers found LPA1 has a "baggy" binding pocket, suggesting that other molecules could bind within it. This route of entry contrasts with that of S1P1, a previously crystalised receptor for a distinct lysophospholipid (called sphingosine 1-phosphate or S1P), which possesses a more linear, rigid binding pocket.
This structural detail enabled the identification of new ligands capable of activating LPA1. Prior studies from the Chun lab had identified protein sequence similarities between LPA1 and cannabinoid receptors, but the commonly known ligands for these receptors did not activate LPA1. The structural data led the researchers to examine modified versions of cannabinoid ligands that might activate LPA1.
The new publication proved this prediction true, providing the first evidence of "cross-talk" between the two systems via a common receptor and establishing a new relationship between two, distinct families of fats—LPAs and the cannabinoids—offering new strategies for understanding and therapeutically accessing these distinct lipid signals.
"This series of structures further illuminates the field of lipid receptors enhancing our understanding of how closely related GPCRs distinguish between very similar endogenous ligands not only through binding interactions but also through route of entry," said Hansen.
"This is a new way of understanding a fundamental interaction between signalling lipids and their receptors," said Chun.
Chun calls the new study the "end of one chapter" his lab started 20 years ago with the identification of LPA1 "and the start of another" through the newly established links to cannabinoid signalling. "This feels good, and I'm happy to have been a part of it," said Chun.
Source: Phys.org © Phys.org 2003 - 2015, Science X network (19/06/15)
Copaxone patent invalidated again(19/06/15)
A U.S. appeals court has again invalidated a patent held by Teva Pharmaceutical Industries on its top-selling multiple sclerosis drug Copaxone, clearing the way for the launch of a cheaper, generic version.
The 2-1 decision by the U.S. Court of Appeals for the Federal Circuit, the nation's top patent tribunal, was a blow to Teva in its seven-year fight against two generic drugmakers over the patent protections for Copaxone.
It is the second time the appeals court has reviewed Teva's patent. In January, the U.S. Supreme Court said the appeals court took the wrong approach in its original decision to cancel the patent.
The extended litigation has benefited Teva, which has been able to continue to sell Copaxone without competition from other manufacturers that would offer steep discounts for their generic versions.
A Teva spokesman said the company is "committed to pursuing all legal pathways, including seeking further appellate review."
Two teams have been developing generic forms of Copaxone: one involving Novartis AG's Sandoz unit and Momenta Pharmaceuticals Inc and another involving Mylan Inc and Natco Pharma Ltd.
Momenta president and CEO Craig Wheeler said in a statement the company was pleased with the decision.
"We look forward to providing patients with a more affordable generic alternative for the treatment of multiple sclerosis," he said.
Teva's patent covered a method of manufacturing the drug. The Federal Circuit said that under the high court's latest standards for determining when a patent is too vague to deserve legal protection, the Teva patent is indefinite.
Teva "has failed to inform with reasonable certainty those skilled in the art about the scope of the invention," the court said.
Teva had sued Sandoz and Mylan in 2008 and 2009 in federal court in New York for patent infringement over their Copaxone copycat versions.
Central to the case was how the district judge interpreted a specific term in a key patent for the drug. The appeals court did not accept that interpretation and invalidated the patent.
The Supreme Court said the Federal Circuit should have deferred to the district judge unless there is evidence of "clear error," sending the case back down.
Source: Reuters © Thomson Reuters 2015 (19/06/15)
In a study published in the journal Nature Communications, researchers have clarified the lifespan of antibody-producing cells and have also identified a novel biomarker that could be used to monitor autoimmune conditions such as multiple sclerosis and lupus erythematous.
The humoral immune response is mediated by cells in plasma and is responsible for fighting infections. Plasma cells secrete antibodies, proteins that are able to identify pathogens and destroy them. However, antibodies with specific characteristics sometimes attack their host tissues causing autoimmune conditions like multiple sclerosis (MS) or lupus erythematosus(SLE).
“Balanced regulation of the production and activity of plasma cells is therefore vital,” Professor Edgar Meinl of the LMU Medical Centre said.
The researchers were able to identify a mechanism of action involved in the regulation of these antibody producing cells’ lifespan. Specifically, the researchers found a cell-surface receptor, called BCMA, can be a useful biomarker for monitoring the severity of autoimmune diseases.
The cells in the plasma are produced by B-cells, which carry certain membrane-bound receptors that are able to identify antigens. When B-cells recognize an antigen, they are able to differentiate it into a clone of plasma cells that secrete the antigen-binding protein in soluble form as antibody. But the life-span of these antibodies is dependent on the BCMA receptor survival.
The extension of the lifespan of the plasma cells is activated by the BAFF and APRIL survival factors, BCMA ligands.. “However, the lifetime of plasma cells cannot be prolonged indefinitely. Otherwise the organism would become swamped with antibodies, increasing the risk of an autoimmune reaction,” Meinl explained.
“We have now shown, in cooperation with colleagues in Munich, Berlin and Stockholm, that the membrane-bound enzyme gamma-secretase acts as a brake on immune reactions by fragmenting BCMA.”
BCMA extended the cell’s membrane and is projected in the extracellular medium. Gamma-secretase removes the exposed portion by cutting the protein inside of the plasma membrane. That this enzyme cleaves the receptor directly was a surprise: “Up to now, it was only known to be involved in the degradation of membrane proteins that had already been cleaved by other enzymes.
“BCMA is the first natural substrate of gamma-secretase to be identified that is directly cleaved by the enzyme,” said Meinl, “and probably reflects the fact that the extracellular segment of the receptor is unusually short.”
The cleaved fragment is constant, and can be detected in fluid of the body as soluble BCMA (sBCMA). The evidence from this new study showed that in patients with Lupus, the sBCMA levels in the blood are high and associated correlated with the disease severity.
“In MS patients sBCMA levels were increased specifically in the cerebrospinal fluid, which bathes the brain and the spinal cord,” said Meinl. “So, sBCMA is an indicator of the intensity of ongoing immune reactions. sBCMA is therefore well suited to serve as an informative clinical parameter for the assessment of the therapeutic effects of different treatment regimes on plasma cells.”
Results from this study could trigger the development of treatments, with both B cells and the BCMA/BAFF/APRIL mechanism being targets for lupus and multiple sclerosis, treatment.
Soure: Multiple Sclerosis News Today © BioNews Services 2015 (19/06/15)
A team led by researchers at the University Hospital Basel in Switzerland say they have found a short period of eight to 12 weeks is the optimal timing to be considered when patients with relapsing-remitting multiple sclerosis (RRMS) are switched from Tysabri (natalizumab) to Gilenya (fingolimod) therapy.
The study was recently published in the journal Neurology.
In this study, researchers conducted a randomised, multicentre, double-blind, placebo-controlled trial (TOFINGO) to determine the optimal timing for initiating Tysabri after discontinuing Gilenya in 142 RRMS patients. The goal was to maintain disease control and avoid potentially harmful additive effects on immune surveillance. The team tested the intervals of eight, 12 and 16 weeks between the last Tysabri infusion and the first Gilenya treatment over 32 weeks. Brain MRI recurrence and clinical disease activity were evaluated.
Researchers found in total, 78.9% (112) of the patients completed the study. The number of active MRI lesions was found to increase according with the duration of the interval between the two therapies. More patients were found to be relapse-free in the eight-week (88%) and 12-week (91%) periods in comparison to the 16-week period (84%). Of the cohort, 68% of the patients experienced mild or moderate adverse events with no major differences between the groups. No unusually severe relapses or opportunistic infections were reported.
The team concluded that patients with RRMS switching from Tysabri to Gilenya therapy should undergo a short period of eight to 12 weeks between therapies, as this time interval is associated with less MRI disease activity than longer periods. The authors suggest that additional studies should be performed to determine whether an interval shorter than eight weeks would further improve disease control with reasonable risks.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (18/06/15)
New research identifies a pivotal gene in multiple sclerosis, linking it to the most important genetic factor that drives the condition.
The human leukocyte antigen class II proteins (HLA-II) is the strongest genetic factor that influences multiple sclerosis. It helps the immune system distinguish the body’s own proteins from foreign proteins, and disturbing this system increases the chances of auto-immune disease. Researchers from The Netherlands and Qatar have discovered how mutation of a single base in the CLEC16A gene interferes with the normal function of HLA-II.
The mutation in CLEC16A results in a faulty HLA-II system, generating blind immune cells that are unable to differentiate pathogen-derived proteins (also known as antigens) from the body’s own proteins. When such blind immune cells escape to the brain, they destroy nerve-insulating myelin, resulting in multiple sclerosis.
The scientists found that silencing the activity of the CLEC16A gene in specific antigen-presenting cells disrupted the ability of HLA-II to display antigens on the cell membrane. Next, they identified that the levels of inactive CLEC16A protein in peripheral blood mononuclear cells of multiple sclerosis patients were two times higher than those of healthy individuals, indicating that CLEC16A has a role in the disease.
“In the future, immunology will continue to unravel what all the risk genes such as CLEC16A really do in the complex adaptive immune system, hopefully aiding the development of new drugs that could interfere with relevant disease-causing pathways,” says lead author Rogier Hintzen from the University Medical Centre, Rotterdam.
Source: Nature Middle East © 2015 Nature Publishing Group (18/06/15)
Clinicians at Ludwig-Maximilians-Universitaet (LMU) in Munich have elucidated a mechanism involved in determining the lifespan of antibody-producing cells, and identified a promising new biomarker for monitoring autoimmune diseases like multiple sclerosis and lupus erythematosus.
The so-called humoral immune response is mediated by plasma cells and plays a central role in combating infections. Plasma cells secrete antibodies - a class of proteins that specifically recognise infectious pathogens and facilitate their destruction. Individual plasma cells make only a single species of antibody that normally recognizes a single structure. Nevertheless, antibodies with certain specificities may erroneously attack the tissues of their host, causing autoimmune diseases such as multiple sclerosis (MS) or lupus erythematosus (SLE).
“Balanced regulation of the production and activity of plasma cells is therefore vital,” says Professor Edgar Meinl (LMU Medical Centre).
Long-term antibody-mediated immunity is provided by so-called long-lived plasma cells, and Meinl and his research team have now identified a novel mechanism involved in regulating the lifespan of these antibody producing cells. This involves the shedding of a particular cell-surface receptor, named BCMA, which is known to bind factors that promote plasma-cell survival. The released segment that is cut off the receptor can be detected in the circulation, and the LMU group has shown that it provides a useful biomarker for monitoring the severity of autoimmune conditions.
Plasma cells develop from progenitors called B-cells that carry specific membrane-bound receptors which recognize foreign proteins termed antigens. When a B cell encounters its cognate antigen, it differentiates into a clone of plasma cells that secrete the antigen-binding protein in soluble form as antibody. How long an antibody-producing plasma cell survives in the body depends largely on the survival receptor BCMA.
When the BCMA binds its ligands, the survival factors BAFF and APRIL, a genetic program is activated which effectively extends the lifespan of the plasma cell.
“However, the lifetime of plasma cells cannot be prolonged indefinitely. Otherwise the organism would become swamped with antibodies, increasing the risk of an autoimmune reaction,” Meinl explained. “We have now shown, in cooperation with colleagues in Munich, Berlin and Stockholm, that the membrane-bound enzyme gamma-secretase acts as a brake on immune reactions by fragmenting BCMA.”
As a so-called transmembrane receptor, BCMA extends through the cell membrane and projects into the extracellular medium. Gamma-secretase removes the exposed portion by cutting the protein inside of the plasma membrane. That this enzyme cleaves the receptor directly was a surprise:
“Up to now, it was only known to be involved in the degradation of membrane proteins that had already been cleaved by other enzymes. BCMA is the first natural substrate of gamma-secretase to be identified that is directly cleaved by the enzyme,” said Meinl, “and probably reflects the fact that the extracellular segment of the receptor is unusually short.”
The cleaved fragment is stable, and can be detected in body fluids as soluble BCMA (sBCMA). Analysis of clinical samples from patients with multiple sclerosis or lupus erythematosus has indicated that the molecule could provide a useful biomarker for autoimmune disease. Lupus is a systemic condition which affects the whole organism. In lupus patients, levels of sBCMA in the blood were found to be abnormally high - and were correlated with the severity of the disease. Multiple sclerosis is an organ-specific disease, which targets the central nervous system.
“Correspondingly, in MS patients sBCMA levels were increased specifically in the cerebrospinal fluid, which bathes the brain and the spinal cord,” said Meinl.
“So, sBCMA is an indicator of the intensity of ongoing immune reactions. sBCMA is therefore well suited to serve as an informative clinical parameter for the assessment of the therapeutic effects of different treatment regimens on plasma cells.”
These findings could facilitate the development of optimized and personalized modes of therapy. Both B cells and the BCMA/BAFF/APRIL system constitute promising targets for the treatment of lupus and multiple sclerosis, as blocking their activity could inhibit the production of the autoimmune antibodies. In the case of lupus, an agent directed against BAFF has already been approved for clinical use. Unfortunately, for unknown reasons, it is effective in only a subset of patients. Further clinical studies on agents that target BAFF, APRIL and their receptors are currently underway. In future, sBCMA could be used to measure and optimize the impact not only of these new therapies but also of already proven treatments, since it enables one to monitor the levels of plasma cells.
Source: News-Medical.net Copyright 2000-2015 AZoM.com Limited (16/06/15)
MediciNova has announced that the ongoing clinical trial of MN-166 (ibudilast) in patients with progressive multiple sclerosis (PMS) has finished the randomisation of 255 patients, exceeding the initial goal of 250 patients.
The National Institute of Neurological Disorders and Stroke (NINDS) aims to conduct an interim analysis of the drug efficacy in the third quarter of 2016, once half of the patients have completed the treatment over 96 weeks.
Yuichi Iwaki, MD, PhD, president and CEO of MediciNova, said: “We are very pleased to have exceeded the enrolment target in this important study. The unmet medical need for progressive MS patients is extremely high as there is no treatment approved for long-term use for these patients. We look forward to providing further updates as the study progresses.”
MN-166 is a first-in-class, orally bioavailable, small molecule glial attenuator that suppresses pro-inflammatory cytokines IL-1ß, TNF-a, and IL-6, and may upregulate the anti-inflammatory cytokine IL-10.
The SPRINT-MS is a Phase 2 Secondary and Primary Progressive Ibudilast NeuroNEXT trial in patients with Multiple Sclerosis designed to evaluate the tolerability, safety, and efficacy of MN-166 (ibudilast) given twice per day to patients with primary or secondary progressive multiple sclerosis (PPMS or SPMS). It involves 28 clinical sites across the United States.
Patients were randomised to receive an inactive control (placebo) or MN-166 (ibudilast) 100 mg/day (50 mg twice daily). For the remainder of the study, patients may be either untreated with long-term disease modifying therapy (DMT) or may continue either glatiramer acetate (GA) or interferon beta (IFNβ-1a or IFNβ-1b) treatment.
The trial involves a controlled randomisation therapy status (IFN/GA verus. no DMT) and disease status (PPMS versus SPMS).
The study primary endpoints are to evaluate the activity of the drug in comparison to the placebo over a period of time of 96 weeks. This will be assessed with magnetic resonance imaging (MRI) using brain parenchymal fraction (BPF). The other primary endpoint involves the assessment of the drug safety and tolerability versus the placebo in with PPMS or SPMS patients. The study secondary endpoints involve imaging analyses of brain and retinal tissue integrity, cortical atrophy disability, cognitive impairment, neuropathic pain and quality-of-life. The study will also include an exploratory analysis of pharmacokinetic and biomarker.
Source: Multiple Sclerosis News Today © BioNews Services 2015 (16/06/15)
‘Positive impact’ of Mediterranean diet(16/06/15)
Several studies have reported that the Mediterranean diet slows cognitive decline and lowers risk of neurodegenerative conditions. While most of the research has been conducted in Mediterranean countries, consumption of the Mediterranean diet by other population groups have provided similar results.
A study on 2,000 New Yorkers who consumed the Mediterranean diet reported lower risk of Alzheimer’s disease; and another study on 1,410 elderly French individuals found slower cognitive decline with higher adherence to the Mediterranean diet. Last year, a review article called the Mediterranean diet a “model” diet for the prevention of Alzheimer’s disease.
While high intakes of cereals, vegetables, legumes, fruits and olive oil that make up the typical Mediterranean diet are recognised to be beneficial, a recent study found long-term consumption of a Mediterranean diet supplemented with extra virgin olive oil or nuts had a positive impact on cognitive function in an older Spanish population. Phenolic compounds present in extra virgin olive oil and nuts may be the components responsible for this positive effect on cognition, according to the investigators of the study.
In an article published in the March, 2015 issue of the journal Molecules, researchers specifically reviewed literature to explain how phenols present in extra virgin olive oil prevent neurodegenerative diseases.
According to the paper, olive oil contains about 230 chemical compounds of which carotenes and phenolic compounds are the main antioxidants. Of the phenols, hydroxytyrosol is the key phenolic compound present mainly in olives and olive products that are, in turn, the chief source of hydroxytyrosol in the Mediterranean diet.
Scientific evidence suggests that, as a potent antioxidant, hydroxytyrosol is not only effective in removing reactive oxygen species produced during oxidative stress, but it may also improve an organism’s defense against oxidative stress.
Oxidative stress, which produces more reactive oxygen species than the body can detoxify, may cause damage to the DNA and body proteins, and may be the origin of neurodegenerative conditions such as Alzheimer’s and Parkinson’s, as well as cancer, atherosclerosis, and diabetes.
Extensive research has identified hydroxytyrosol from olive oil to possess antioxidant, antimicrobial, and antidiabetic abilities. Additionally, hydroxytyrosol may provide protection against heart diseases and play a role in preventing or slowing the growth of tumors.
Research carried out in vitro and ex vivo to determine hydroxytyrosol’s role as a neuroprotective agent shows that hydroxytyrosol from olive oil protects cells from oxidative stress, improves resistance to oxidative stress, lowers incidence of brain cell death, and reduces neurotoxicity and DNA damage.
Furthermore, in some in vitro studies, hydroxytyrosol has been associated with the nuclear factor E2-related factor 2 (Nrf2) and Antioxidant Responsive Elements (ARE) neuroprotective pathways. The Nrf2 plays a positive role in regulating antioxidant response elements, which in turn regulate gene expression of several phase II detoxifying enzymes.
Supplementing the diet of mice with extra virgin olive oil and hydroxytyrosol enhanced cognitive function, and reversed oxidation, learning and memory damage. In another study, EVOO and hydroxtyrosol acted as brain antioxidants and provided protection against oxidative damage in mice with Huntington disease.
While in vitro and in vivo studies on animal models have linked hydroxytyrosol to improved health and cognition, there are very few studies on the effect of hydroxytyrosol in humans. So far, only three clinical trials on the role of hydroxytyrosol on breast cancer prevention; the effect of hydroxytyrosol supplements on multiple sclerosis; and its influence on phase II enzymes are underway.
Although more research is needed to establish the role of EVOO hydroxytyrosol in preventing neurodegenerative diseases, there is ample evidence that suggests that consuming a Mediterranean diet is beneficial for cognitive health.
Source: Olive Oil Times © 2015 Olive Oil Times (16/06/15)
Researchers around the world have sequenced the genomes of patients living with from common, multi-gene diseases, looking for common mutations in their control regions. However these studies produce hundreds of mutations, many of which prove to be benign.
Now a research team led by associate professor of biomedical engineering, Michael Beer, have generated a new computational formula for predicting which mutations in control regions will wreak the most havoc. Their research has been published in Nature Genetics.
Their focus was on finding genetic control regions in stretches of DNA positioned near most genes. These regions act like dimmer switches which control the amount of each protein produced. Mutations in control regions generally have more subtle effects than mutations in genes themselves, but they can contribute to common, genetically complex, chronic diseases such as diabetes.
Beer’s team first “trained” their computer program to recognise and measure DNase sensitivity in susceptible genetic control regions. DNase is an enzyme that cuts DNA wherever it is not tightly wound. The openness of particular sequences of DNA varies among different types of cells and only control regions with open DNA can be active. How vulnerable certain stretches of DNA are to DNase is therefore an indication of which control regions are important in a given cell type.
They then computationally simulated “mutating” every DNA letter in turn and recalculated each section’s contribution to DNAse sensitivity. The larger the change in sensitivity after a given mutation, the more likely it is that that mutation will effect gene activity levels in the cell, Beer says.
The team compared these computer predictions to the known effects of some mutations, and to the predictions made by alternative programs. When the programs’ “rules” were set to be equally thorough in their searches, Beer’s program was 56 percent accurate — 10 times more accurate than the next best program.
Beer worked with Andrew McCallion, PhD an associate professor at the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine to further test the computational formula to predict the impact of mutations in the control regions for two pigment-related genes in mouse skin cells. They found that there was a strong correlation between the program’s prediction and the actual change experienced by the cells.
Dr. Beer and his team also tested their formula in mouse and human liver cells, and in human leukemia cells, and got similar results. They also tested their formula on three control region mutations already known to affect cholesterol levels, hemoglobin levels and prostate cancer. Again they found that these mutations drew higher computer scores than other mutations in the same control regions.
Finally, the team examined the control regions for T helper cells, a type of immune cell that can contribute to autoimmune diseases. Their calculations identified 15 different control region mutations associated with nine different immune system disorders from allergies to multiple sclerosis and Crohn’s disease. The research honed in on the exact genetic mutation that mattered. Beer says, “The next step is to test gene activity levels in patients and find out if our predictions were right. If so, it should help us determine how the activity is being perturbed and how we can fix it.”
This computational analysis can be repeated on many other diseases to provide timesaving insights for each.
Other authors of the report include Dongwon Lee, David Gorkin, and Maggie Baker, of the Johns Hopkins University School of Medicine, and Benjamin Strober and Alessandro Asoni who contributed to the project while undergraduates in the Department of Biomedical Engineering.
Source: Johns Hopkins Biomedical Engineering © 2015 Johns Hopkins Department of Biomedical Engineering (16/06/15)
Gilenya safety update issued by Novartis(12/06/15)
On 05 June 2015, Novartis issued the following statement:
‘Novartis has been informed of a patient with progressive multifocal leukoencephalopathy (PML). The patient had been diagnosed with ulcerative colitis (an autoimmune bowel disease) in 2011 and had been treated with oral mesalazine since February 2011. At the end of 2012, the patient started treatment with Gilenya® (fingolimod) for the management of relapsing MS (RMS).
‘The patient is currently hospitalised. The diagnosis was based on suggestive clinical symptoms, MRI findings and tests for JC (John Cunningham) virus. Novartis is in active discussions with external advisors and Health Authorities to review details of this case and the role of various risk factors contributing to the development of PML.
‘Patient safety is of paramount importance for Novartis, and we monitor all aspects of patient safety to the highest standards.
‘With more than 119,000 patients treated with Gilenya and 218,500 patient years of exposure in both clinical trials and post-marketing setting, Novartis continues to stand behind the positive benefit-risk profile of Gilenya in relapsing MS.’
Source: Novartis copyright 2015 www.novartis.com/news/statements/gilenya-safety-update (05/06/2015)
With genetic roots of many autoimmune diseases pinpointed, scientists are zeroing in on the variety of molecular mechanisms triggered by these harmful variants. A team led by Yale School of Medicine researchers has implicated a central regulator of inflammation as a cause of many cases of multiple sclerosis — and intriguingly, the researchers note — ulcerative colitis as well.
The study was published in the June 10 issue of the journal Science Translational Medicine.
‘After identifying the genes that cause MS, we are starting to generate a comprehensive roadmap of the how these genes operate together in allowing immune cells to become activated and attack the myelin,’ says David A. Hafler, the William S. and Lois Stiles Professor of Neurology and Immunobiology at Yale and chair of Yale’s Department of Neurology.
In 2014, a consortium of researchers identified genetic variants that play a role in onset of 21 different autoimmune diseases. Ninety-seven variants were associated with multiple sclerosis. The new Yale research led by Hafler and first author William J. Housley shows that 17 of these MS variants affect the NFkB pathway, which controls a host of immune system responses to environmental threats, and that one variant associated with MS near the NFkB gene profoundly increased gene activity.
The findings illustrate the complexity of individual diseases like MS, in which variants can contribute to small increases in risk of disease through different molecular mechanisms. They also illustrate how same molecular pathways, such as NFkB, can trigger a variety of autoimmune diseases with fundamentally different symptoms — such as MS and ulcerative colitis.
‘Identifying these like-minded genes that by themselves contribute only a small risk to disease but together lead to major alterations in immune function may allow a more precise approach in deciding which drug should be used to treat patients,’ Hafler said.
Primary funding for the research came from grants from the National Institute of Health and the National Multiple Sclerosis Society.
Source: By Bill Hathaway, YaleNews copyright 2015 news.yale.edu (10/06/2015)
For the first time since 2009, a group of experts have published revisions to the guidelines for magnetic resonance imaging (MRI) in multiple sclerosis, which stress the need for a standardised protocol in the diagnosis and follow-up of this patient population. Details of the revised guidelines were provided in a presentation at the Consortium of Multiple Sclerosis Centers 2015 Annual Meeting.
‘Over the last 10 years, technology has improved such that we can get higher-quality imaging. As a result, if we can get people to use a standardised protocol, we can use that higher-quality imaging to accurately compare over time,’ lead guideline author Anthony Traboulsee, MD, of UBC Hospital in Vancouver, Canada, told Neurology Advisor. ‘There has also been more evidence that … new disease activity can influence treatment decisions [and] can let us know whether patients are on sufficient therapy or if they need an escalation of their therapy. That is probably the most dramatic change in the field — there is now more of a consensus that MRI is very useful and not just sort of useful.’
According to guideline author David K.B. Li, MD, of the UBC MS/MRI Research Group and UBC Hospital in Vancouver, Canada, the goal of these new updates was to standardise as much as possible, given the limitations that there will be technical improvements.
‘The aim was to make things as backwardly and forwardly compatible as possible, so that you can compare and be absolutely certain that a change in terms of a new abnormality is because there has been a change as opposed to anything technical,’ Li said.
In addition to reemphasising the importance of obtaining the highest quality of images possible, the new set of guidelines also stress that scans should be obtained as similarly as possible from one study to the next. ‘In other words, [scans] should be reproducible in terms of brain coverage, so the whole brain needs to be covered and in terms of position of the scan,’ Li said.
A key change with the updates, he said, is that previously, physicians were allowed to obtain scans at a 5 mm slice thickness to save time. ‘But the change now with the most recent revision is that 3 mm is what is recommended,’ he said.
Another change involves the acquisition of scans in three rather than two dimensions, or volume instead of a slice.
‘When you obtain in a volume, you can still determine the intervals of those planes under review,’ Li said. ‘The three-dimensional acquisitions tend to be obtained in 1 to 1.5 mm intervals — which is where the field is today.’
Traboulsee added that the guidelines have also introduced a new quick sequence to look for a rare but serious complication of MS treatment called progressive multifocal leukoencephalopathy (PML).
‘With the more effective drugs we now have for MS, they are really good at controlling MS but they sometimes carry significant risks, such as [PML],’ he said. ‘We now have provided guidance on how to monitor for [PML], so that if it's detected early, we might be able to prevent death.’
Going forward, although acknowledging that these guidelines will likely change again as technology continues to get better, Traboulsee said they have designed this protocol to have a timelessness so that any future changes will be able to take advantage of the data.
‘The data collection now won't be lost because there is a new technique in the future,’ he said. ‘We have taken that into consideration such that all data collection now will be useful with any changes to the protocol in the future.’
The revised guidelines are scheduled for publication in the American Journal of Neuroradiology.
Source: Neurology Advisor copyright 2015 www.neurologyadvisor.com (08/06/2015)
In a recent review published in the journal Seminars in Arthritis and Rheumatism, German researchers explored the complexity of interwoven pathways of osteopenia, and how it relates to diseases such as MS.
Osteopenia is a bone condition characterised by a decreased density of bone, which leads to bone weakening and an increased risk of breaking a bone (fracture). Osteopenia and osteoporosis are related conditions. The difference between osteopenia and osteoporosis is that in osteopenia the bone loss is not as severe as in osteoporosis. This means that someone with osteopenia is more likely to fracture a bone than someone with a normal bone density but is less likely to fracture a bone than someone with osteoporosis.
The condition is common in patients with syndromes such as ankylosing spondylitis, rheumatoid arthritis, psoriasis, pemphigus vulgarism, systemic lupus erythematosus, multiple sclerosis, and inflammatory bowel diseases.
People with MS have multiple risk factors for osteopenia. In the pathological lesion of the brain and spinal cord that characterises MS, there are differences in the disease according to the evolution of the lesion (i.e., progressive MS vs relapsing remitting), including residual mobility and functionality, the ability to walk and stand, and drug treatment (i.e., corticosteroid therapy, interferon therapy). In addition, there are differences in the degree of spasticity experienced by people with MS, a complication caused by alterations in the nerve impulses to the muscles resulting in spasms and stiffness. Disturbed coordination and balance can cause frequent falls.
There are several studies of bone mass loss in women with MS. Women with serious disabilities have low bone density related to the lack of activity (reduced mobility, reduced loading on bone) and worsening of the disability. Bone loss is associated with an activation of the immune system or inflamm-aging in the form of chronic active and acute, or chronic smoldering inflammation, bone loss is typically discussed to be an ‘accident of inflammation.’
In their study titled ‘Evolutionary medicine and bone loss in chronic inflammatory diseases-A theory of inflammation-related osteopenia,’ Rainer Straub from the Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, University Hospital Regensburg in Germany and colleagues examined articles published in PubMed regarding the topic of osteopenia and diseases such as MS.
The researchers determined that evolutionary medicine (which include energy regulation and neuroendocrine regulation of homeostasis and immune function) reveals that adaptive programs for acute inflammation are wrongly used in chronic inflammation. One of these adaptive programs in acute inflammation is provision of calcium and phosphorus from bone to the non-skeleton tissues. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program.
According to the researchers, while these considerations might explain the deeper meaning of bone resorption in inflammation, the final answers to these questions remain dependent on finding the major molecular pathways to better treat these disease sequelae. As the researchers concluded, their review aims at exploring the idea that sometimes the critical pathways leading to osteopenia can be outside usual mainstream thinking. It also demonstrates that osteopenia must be a multifactorial affair — all insights that could shape the development of next-generation treatment approaches for MS patients suffering from bones loss.
Source: Multiple Sclerosis News Today copyright 2015 multiplesclerosisnewstoday.com (09/06/2015)
The most common form of MS is relapsing-remitting MS (RRMS), in which periods of mild or no symptoms are interspersed with periods of more severe symptoms, called relapses. RRMS can change into a progressive form where symptoms worsen over time without any symptom-free periods. RRMS can be treated with medications that suppress the immune system and reduce inflammation. However, these drugs can cause serious side effects.
High Dose immunosuppressive therapy with autologous hematopoietic cell transplant has been found to be a promising tool to stop the progression of MS in patients with early stage RRMS. In this treatment, a patient’s hematopoietic stem cells (HSCs)—precursor cells that develop into blood cells—are collected. High-dose chemotherapy and other drugs are then used to deplete the patient’s immune system. Finally, the patient is infused with his or her own HSCs, which develop into red and white blood cells to re-establish the patient’s immune system.
Three years after HDIT/HCT treatment, nearly 80% of trial participants had survived without an increase in disability, relapse of MS symptoms. Patients didn’t receive any MS drugs during those 3 years. ‘These promising results support the need for future studies to further evaluate the benefits and risks of HDIT/HCT and directly compare this treatment strategy to current MS therapies,’ says NIAID Director Dr. Anthony S. Fauci.
Another collaborative study was conducted between Northwestern’s Feinberg School, University Hospital Zurich in Switzerland and University Medical Center Hamburg-Eppendorf in Germany. A phase 1 clinical trial for the first treatment to reset the immune system of multiple sclerosis (MS) patients showed the therapy was safe and dramatically reduced patients’ immune systems’ reactivity to myelin by 50 to 75 percent.
In this study, the researchers filtered the white blood cells out of the patients’ blood, processed them and combined them with myelin antigens (the parts of the myelin protein that the immune system reacts to). They then injected billions of the processed white blood cells, packed with myelin antigens, back into the patients. The cells entered the spleen, which filters the blood and helps the body eliminate old and dying blood cells. It is during this process that immune cells recognize the myelin antigen as harmless and immune tolerance develops. This was confirmed in the patients by immune assays, say the researcher's team in Hamburg.
'The therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells,' said Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. 'Our approach leaves the function of the normal immune system intact. That's the holy grail.'
Miller's research represents several pillars of Northwestern’s Strategic Plan by discovering new ways to treat disease in the biomedical sciences and translating those discoveries into ideas and products that make the world a better place for everyone.
Source: biotechin.asia Copyright biotechin.asia (07/06/2015)
Review suggests PEG-IFN therapy for Relapsing-Remitting multiple sclerosis significantly reduces relapse rates(08/06/15)
A study recently published in the journal PLoS One compared the use of a specific treatment based on interferon beta-1a with other approved injectable therapies in patients with relapsing-remitting multiple sclerosis (RRMS). The study is entitled ‘A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis’ and was conducted by an international research team led by researchers at Tolley Health Economics Ltd. in the United Kingdom and Biogen Idec Inc.in the United States.
The most frequent form of the disease is the RRMS, which is clinically characterized by recurring episodes of neurological symptoms. Currently, interferon-beta (IFN-beta) immunomodulatory drugs are the most widely prescribed therapy for the relapsing-remitting form of the disease. It is thought that IFN-beta drugs affect the course of the disease through involvement of the immune system and by preventing inflammation and demyelination. IFN beta-1a treatment has been shown to reduce the relapse frequency and the risk of confirmed disability progression (CDP).
The pivotal randomized, double-blind, 2-year study Phase 3 ADVANCE trial assessed the efficacy of subcutaneous pegylated IFN-beta-1a (peginterferon beta-1a [PEG-IFN]) treatment at a dose of 125 μg, every two or four weeks in RRMS patients. A network meta-analysis (NMA) was performed in order to evaluate PEG-IFN’s relative efficacy, safety and tolerability in comparison to other injectable RRMS therapies. Systematic searches on Embase, MEDLINE and the Cochrane Library were conducted, as well as hand-searched conference proceedings from pertinent annual symposia. The studies included in the analysis were based on randomised controlled trials assessing one or more first-line therapies in patients with RRMS.
Researchers found that PEG-IFN therapy every 2 weeks was able to significantly reduce the relapse rate, as well as 3 and 6 months CDP in comparison to the placebo drug after one year of treatment. When compared to other injectable drugs, PEG-IFN was found to have a similar efficacy with no statistically significant differences. The safety profile of PEG-IFN at 125 μg every 2 weeks was found to be comparable to other injectable treatments.
The team concluded that PEG-IFN therapy has an overall safe profile and a similar efficacy to other RRMS treatments, as assessed by annualised relapse rate and 3- and 6-months CDP. PEG-IFN every 2 weeks allows a reduction of up to 93% in the number of injections needed, a fact that may strongly improve patient adherence and compliance with this particular treatment, ultimately improving the patient’s clinical outcome and overall quality of life. The team suggests that PEG-IFN therapy 125 μg every 2 weeks regimen represents a valuable treatment option for patients with RRMS.
While the results of this review are potentially helpful for those diagnosed with RRMS, multiple sclerosis patients with the progressive forms of the disease are still in need of effective, approved therapies. Currently in the US, interferon-based therapies for RRM are frequently re-appropriated for PPMS and SPMS, albeit with only modest effectiveness. It remains to be seen if this current finding will have any impact on treating progressive MS.
Source: Multiple Sclerosis News Today Copyright multiplesclerosisnewstoday.com (08/06/2015)
FDA’s approval of the first generic version of Copaxone (glatiramer acetate injection) for treating patients with relapsing forms of multiple sclerosis has industry insiders contemplating the impact on the generics market as well as payer coverage strategies.
Manufacturer Sandoz with Momenta will market generic glatiramer acetate injection, or Glatopa, in a 20-mg/1-mL daily injection. Currently 45% of Copaxone users are on the same daily dose, while 65% opt for the long-acting 40-mg/mL three times a week injection. There is no long-lasting generic version.
‘The price of Copaxone has increased...since its launch in 1996 when the cost for a year of treatment was $9,000,’ according to Barbara Gilmore, Life Sciences Senior Industry Analyst, Frost & Sullivan. ‘In 2014, a year of treatment cost $60,000.’
The approval increases the competition in this already competitive space, according to analysts. Generic Glatopa will reduce the annual cost of daily treatment of MS for some patients and may draw back some of the patients who recently switched to the long-acting version of the branded product.
‘The expectation is that it will drive down costs for MS treatments, but by how much is yet to be determined,’ says Anna Goldbeck, a principal in the National Pharmacy Practice at Buck Consultants at Xerox.
If the two products demonstrate similar comparative effectiveness, the adoption of formulary and utilisation management controls for three times per week 40-mg form of Copaxone and the generic version of the daily 20-mg form of Copaxone will boil down to net unit costs for the products, according to Ruth Ann C. Opdycke, PharmD, MS, president, TPG Healthcare Consulting LLC.
Source: Managed Healthcare Executive Copyright managedhealthcareexecutive.modernmedicine.com (05/06/2015)
Multiple sclerosis patients with comorbidities may be at a greater risk of disruptive pain, according to data presented at the Consortium of Multiple Sclerosis Centers 2015 Annual Meeting.
Although pain is a concern for all people with MS, comorbidities can affect disease management and may influence pain. Kirsten M. Fiest, PhD, of the University of Manitoba in Canada, and colleagues sought to better understand the relationship between comorbidity and pain in MS patients.
Fiest and colleagues collected data from 949 participants with confirmed MS from July 2010 - March 2011. Participants, who were mostly female (75.2%) and white (85.4%), completed the Health Utilities Index (HUI-Mark III) and a comorbidity questionnaire during three clinic visits over two years. Based on the HUI's five-point pain scale, participants were divided into two groups: those with and without pain that disrupts normal activities.
At baseline, 41.5% of participants had at least one comorbid condition, with 40.5% reporting prevalence of disruptive pain. Incidence of disruptive pain at years one and two were 12.1 and 12.7 per 100 persons, and baseline effects on pain from peripheral vascular disease, fibromyalgia, rheumatoid arthritis, IBS, IBD, migraine, COPD, depression, anxiety, hypertension, and high cholesterol were observed at all time points (P-0.006).
On an individual level, significant effects on the presence of worsening pain were seen in patients with bipolar disorder (OR: 3.05 95% CI: 1.32-7.05), lupus (OR: 2.82 95% CI: 1.26-6.29), COPD (OR: 1.50 95% CI: 1.08-2.09), anxiety (OR: 1.49 95% CI: 1.07-2.08), and autoimmune thyroid disease (OR: 1.40 95% CI: 1.00-1.97).
The researchers recommended that further study of the associations between pain and comorbidities in MS may yield better management of the disabling pain symptoms.
Source: Neurology Advisor copyright www.neurologyadvisor.com (04/06/2015)
First MS care awards launched(05/06/15)
The first ever awards specifically for nurses and other health professionals working with patients with multiple sclerosis have been launched.
The QuDos awards are intended to recognise “innovation and excellence” in the management and service delivery of care for MS patients.
The QuDoS awards are a partnership between the MS Trust and pharmaceutical industry PR firm Pharmaphorum, backed by a number of drug companies including Genzyme and Novartis.
The awards are open to MS nurses, general nurses working with people living with MS, and other health professionals.
A statement on the awards website said: “Whether you are working in a major centre or providing an MS service in a rural community setting, the QuDoS in MS Awards are a chance to gain recognition for the difference you make to people with MS or nominate others for their great work.”
In total there are 10 categories. The entry deadline is September 3, 2015, and winners will be announced at a ceremony on November 7.
The MS Trust said it was “pleased to support the launch of the first ever awards recognising the contribution of healthcare professionals to improving care for people living with MS”.
Amy Bowen, director of service development at the MS Trust and herself a nurse, said the charity was “proud” to be associated with the new awards.
“These awards will enable teams and individuals across the UK to be recognised for their efforts in improving the quality of care for people living with multiple sclerosis,” she said.
Source: Nursing Times © 2002-2015 EMAP Publishing Limited (05/06/15)
Test could find complete virus history(05/06/15)
A new blood test can find just about every virus you ever caught — in a single drop of blood.
Doctors are hoping the test might be used to find out whether viruses might cause a range of chronic diseases such as diabetes or heart disease, and to see whether infections early in life can affect your immunity later.
"VirScan is a little like looking back in time. Using this method, we can take a tiny drop of blood and determine what viruses a person has been infected with over the course of many years," said Stephen Elledge, a Howard Hughes Medical Institute researcher at Brigham and Women's Hospital in Boston, who led the study.
"Right now, a physician needs to guess what virus might be at play and individually test for it. With VirScan, we can look for virtually all viruses, even rare ones, with a single test."
The test looks for the body's immune response to viruses. It finds antibodies that keep the viruses from coming back, which can stay circulating in the blood for years.
Elledge thinks the test will cost about $25 (£16) to run.
There are thousands of viruses, from rhinoviruses and adenoviruses that cause the common cold, to the human immunodeficiency virus that causes AIDS. A total of 206 different species of viruses are known to infect people, and each species has various strains.
Most blood tests are designed to look for one particular virus at a time. Elledge and his colleagues wanted to design a test that would find all the viruses — a collection called the virome.
They developed the test using bacteriophages, which are viruses that attack bacteria. They engineered different bacteriophage to make a little piece of protein from more than 1,000 known viruses.
The test goes into a drop of blood, which is enough to carry all the antibodies trained to recognize a virus that's infected someone — or those activated by a vaccine.
Writing in the journal Science, the team said they tested blood samples from 569 people from the United States, Peru, South Africa and Thailand.
On average, people had antibodies against 10 species of virus. There were a few people who'd been infected with many different viruses — five people had antibodies against 62 species, and two had been infected with 84 different species.
It's well known that viruses can cause disease. The human papilloma virus (HPV), for instance, causes cervical cancer, as well as head and neck cancer and cancers of the genitals. Epstein-Barr virus, which infected 88 percent of the volunteers, is linked to lymphoma and is suspected of causing some cases of stomach cancer. It's also been linked with multiple sclerosis.
Enterovirus D-68, a distant relative of polio, concerned doctors when it made an unusual resurgence last year and appeared to cause a mysterious polio-like syndrome in a few children.
Having a test that can look for all sorts of viral infections at once can help researchers tighten up these links, and also help them find possible other links between viruses and long term health.
It's not perfect, however, and Elledge said some viruses didn't turn up as often as they expected.
"For example, the frequency at which we detect influenza (53.4 per cent) and poliovirus (33.7 per cent) is lower than expected given that the majority of the population has been exposed to or vaccinated against these viruses," they wrote.
It also only found that about 24 percent of the people tested had antibodies to chickenpox, also called varicella, which is far fewer than expected.
But when they tried the test against people who knew they had HIV and hepatitis C, the test was 95 to 100 percent accurate. "We didn't falsely identify people who were negative," Elledge added. "That gave us confidence that we could detect other viruses, and when we did see them we would know they were real.
"Although we detected antibody responses to rare and highly virulent viruses such as Marburg and bat lyssavirus, they were found in less than 0.4 percent of the population.”
Elledge's team says the test could easily be expanded to include other human pathogens such as bacteria, fungi, and protozoa. The test might also be used to find out if there are consequences of being infected with two or more particular viruses.
Source: NBC © NBCNews.Com (05/06/15)
Caitlin Dionne, RN, of Lahey Outpatient Centre in Massachusetts, and colleagues developed the MS Treatment Adherence Questionnaire in order to draw more honest answers about treatment compliance out of MS patients, noting that patient response to direct physician inquiry is often questionable.
The questionnaire included six questions related to DMT use: number of missed doses in four weeks; reason dose was missed; perceived side effects; ease of administration; and medication satisfaction. In the study, medication types were divided into subcutaneous or intramuscular (SC/IM), monthly IV injections, or oral DMTs.
Between October and November 2014, Dionne and colleagues collected data from 209 patients. Eighty nine patients (42.5 per cent) were on oral medication, 90 (43 per cent) on SC/IM, and 30 (14.5 per cent) on IV infusion. Among patients on oral DMTs, 45 per cent reported no missed doses, compared to 70.8 per cent of SC/IM and 93.3 per cent of IV infusion patients. Ease of taking the medication did not seem to affect treatment compliance, as 77 per cent, 60 per cent, and 33 per cent of patients on oral, IV, and SC/IM injections reported ease of use, respectively. Among patients taking oral and SC/IM injections, forgetfulness was among the top reasons for missing a dose.
As for how side effects may affect compliance, the majority of patients on IV infusion did not experience side effects, while 18.6 per cent of orals and 20.2 per cent of SC/IM patients reported them.
The authors speculated that side effect profiles related to oral DMTs may be at the centre of the reason for the poor compliance rates among oral users, despite oral DMTs' association with ease of use.
In another study, researchers from Washington, D.C.'s Veterans Affairs Medical Centre evaluated the effects of using a telehealth program on DMT compliance. The preliminary study, which followed 30 patients for six months, compared compliance rates with use of a MS-specific home automated telehealth system (MS HAT) to treatment as usual.
Patients — all who used SC/IM injections — who were assigned to the MS HAT group received text or email reminders to administer their medication through the system, which supports patient self-management, patient-provider communication, and patient education.
Although the MS HAT administration reminders was negatively correlated with syringe counts, the authors noted that as self-report adherence improved, the number of syringes collected increased. Overall, the results suggest that monitoring self-reported adherence through an automated teleheath system is a reliable method of assessing DMT adherence.
Source: Neurology Advisor © 2015 Haymarket Media, Inc. (04/06/15)
Longer-term data indicate the effects of Lemtrada are long-lasting in patients with relapsing-remitting multiple sclerosis (RRMS).
An extension study showed patients treated with the drug remained free of new MRI disease activity for up to four years, even though most of them had not had a treatment for 3 years.
The rate of brain atrophy also remained low in these patients at the end of four years.
The drug, which targets the CD52 antigen found in abundance on B cells and T cells, received US Food and Drug Administration approval in November to treat patients with MS in whom two other therapies had failed. The drug depletes these B and T cells, which are thought to cause the damaging inflammatory process in MS, before these cells "come back and repopulate," said MS expert Ann Bass, MD, Neurology Center of San Antonio, Texas.
It's believed this distinctive pattern of B and T cell repopulation may rebalance the immune system.
But the drug carries risks for significant adverse effects, which can include infusion-associated reactions such as itchiness, gastrointestinal adverse effects, kidney disease, infections, and thyroid disorders, that require "heavy" laboratory monitoring, said Dr Bass.
For this reason, Lemtrada is typically used only in patients with highly active disease. "Candidates for this treatment include those who have already had a relapse on their current therapy, those who have MRI activity that's breaking through on the current therapy, and those who have disability progression that's worsening even on current therapy," said Dr Bass.
The two-year multicenter, rater-blinded study, CARE-MS II, one of two pivotal trials for the drug, showed that compared with patients with RRMS taking subcutaneous interferon β-1a, 44 μg, those who had received a baseline Lemtrada treatment (12 mg) and another treatment at 12 months had a 49 per cent decreased annualised relapse rate and a 42 per cent decrease in six-month sustained accumulation of disability.
The drug seems to have "this nice control of the disease in the absence of ongoing treatment, which is quite novel," commented Anthony Traboulsee, MD, University of British Columbia, Canada.
"One of the important questions is how long will this last before there is some breakthrough disease activity."
That, he said, was the point of the open-label extension study.
At the end of the original two-year trial, patients who were receiving interferon could opt to begin taking the drug, and those who were already taking it could receive additional treatments — a third and fourth cycle — as needed.
For this analysis, MRI outcomes included gadolinium (Gd)-enhancing, new or enlarging T2 hyperintense and new T1 hypointense lesion activity; freedom from MRI activity (absence of Gd-enhancing and new or enlarging T2 lesions); and brain volume loss measured by change in brain parenchymal fraction (BPF).
Of the original study cohort, 393 (92.9 per cent) patients entered the extension phase. At four years, 67.7 per cent of these patients had received only the initial two courses of treatment, 24.2 per cent had needed one additional course, and 7.4 per cent had received two additional courses.
The proportions of patients free of Gd-enhancing lesions were 86.5 per cent and 89.1 per cent at years three and four respectively. The numbers of new or enlarging T2 (69.0 per cent and 70.3 per cent) or new T1 lesions (87.5 per cent and 86.3 per cent) remained stable.
Most patients were free of MRI activity at year three (68.4 per cent) and year four (69.9 per cent).
"What makes it novel is the fact you can go for years and years after your treatment without having new MRI activity," commented Dr Traboulsee.
The durable effects of the drug may be due to the distinct pattern of lymphocyte depletion and repopulation following treatment, said Dr Traboulsee.
Source: Medsape Multispeciality © 1994-2015 by WebMD LLC (04/06/15)
New MS drug shows good results (04/06/15)
Daclizumab HYP (Zinbryta) may have an advantage over interferon-beta-1a (Avonex) in terms of patient-centred functional outcomes in multiple sclerosis (MS), researchers claim.
In a post-hoc analysis from the DECIDE trial, patients on Daclizumab HYP had greater improvements in specified measured areas than those on the interferon-beta-1a, Michael Kaufman, MD, of Carolinas Health Care, and colleagues reported at the Consortium of Multiple Sclerosis Centers meeting.
The DECIDE trial previously found Daclizumab HYP cut relapse rates and disability progression to a greater extent than interferon-beta-1a.
For the post-hoc analysis, Kaufman and colleagues looked at data from a 1,841-patient trial that randomised relapsing-remitting patients on both drugs. They assessed outcomes on the Multiple Sclerosis Functional Composite (MSFC) test, which includes three standard MS ambulatory assessments -- the Timed 25-Foot Walk test (T25FW), the Nine-Hole Peg Test (9HP), and the Paced Auditory Serial Addition Test-3 (PASAT-3). They also assessed cognitive function using the Symbol Digit Modalities Test (SDMT).
They found that over the 96-week study period, the median z-score change from baseline in the MSFC was significantly greater in the daclizumab HYP group.
The authors also reported significantly greater improvements in cognition.
"Over two to three years, daclizumab HYP showed greater improvement than interferon-beta 1a in patient-centred measures of functional disability," Kaufman said. "This supports earlier findings that daclizumab HYP demonstrated superior efficacy to interferon beta-1a across key clinical and radiographic MS outcome measures. It has the potential to be a new therapeutic option for relapsing-remitting MS."
The HYP at the end of the drug's name stands for high yield process, which is intended to distinguish the drug from an earlier formulation sold as Zenapax. Biogen and AbbVie recently filed the biologics license application (BLA) for daclizumab HYP.
Source: MedPage Today © 2015 MedPage Today, LLC (04/06/15)
People with multiple sclerosis may have lower rates of vascular comorbidities, including hypertension, diabetes, and hyperlipidemia, results from a study indicate.
Elizabeth Triche, PhD, of St. Francis Hospital and Medical Center in Hartford, Connecticut, and colleagues looked at vascular complications in a single-center cohort of multiple sclerosis (MS) patients in the general population. The results were presented in a poster session at the Consortium of Multiple Sclerosis Centers 2015 Annual Meeting.
Among 200 MS patients (mean age 45 years) with a mean disease duration of eight years and mean body mass index (BMI) of 28 kg/m2, rates of vascular comorbidities were similar to the general population, however, upon further analyses, gender and age-specific differences emerged.
In women aged 20 to 44 with MS, 4.1% had hypertension compared to 8.7% of the general population, and in women aged 45 to 64, hypertension rates were 25% compared to 39.5% in the general population. A similar trend was seen for hyperlipidemia, with 23.5% of women with MS aged 45 to 64 with hyperlipidemia compared to 42.4% of the general population.
The opposite trend was seen for diabetes in women with MS, where compared to the general population, 4.1% of women with MS aged 44 and under had diabetes compared to 1.7% of the general population.
Among men with MS, rates of hypertension and hyperlipidemia were similar across age groups in both cohorts; however men with MS (all age groups) had lower rates of diabetes than the general population.
The mechanism of the relationship isn't fully understood, however some have suggested that the lower rates of vascular comorbidities among people with MS is related to MS patients having greater access to healthcare.
Triche EW et al. Poster EG08. Vascular Comorbidities Among Patients with Multiple Sclerosis at a Comprehensive Care Center. Presented at: Consortium of Multiple Sclerosis Centers Annual Meeting 2015; May 27-30, 2015; Indianapolis, IN.
Source: Neurology Advisor © 2015 Haymarket Media, Inc (02/06/15)
In a discovery that could overturn decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist.
That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer's disease to multiple sclerosis.
"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG).
"It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions.
"We believe that for every neurological disease that has an immune component to it, these vessels may play a major role. Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component."
Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis' lab: "The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation - and they've done many studies since then to bolster the finding - that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."
The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis' lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges - the membranes covering the brain - on a single slide so that they could be examined as a whole. "It was fairly easy, actually," he said. "There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn't have worked."
After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: "I called Jony [Kipnis] to the microscope and I said, 'I think we have something.'" As to how the brain's lymphatic vessels managed to escape notice all this time, Kipnis described them as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."
"Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris," Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the "phenomenal" surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.
The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer's disease. "In Alzheimer's, there are accumulations of big protein chunks in the brain," Kipnis said. "We think they may be accumulating in the brain because they're not being efficiently removed by these vessels." He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.
Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (02/06/15)
Speaking at the 2015 Annual Meeting of the Consortium of Multiple Sclerosis Centers in Indianapolis, Indiana, Mr Samuel F. Hunter, MD, PhD, president of the Advanced Neurosciences Institute in Franklin, Tennessee, gave a presentation on outcomes in patients with relapsing multiple sclerosis (MS) treated with Lemtrada (alemtuzumab).
He said the first trial began 24 years ago, so primary care physicians may want to share this with their MS patients who are concerned about trying a “new” drug.
Hunter said Lemtrada is thought of as a “permanent” disease-modifying therapy.
“It cleans the immune system up, both the B and T cells. Transiently, it removes a lot of these cells and lets the immune system reconstitute. No one knows how it can make MS better yet, but the immune system is different,” he said.
At the same time, there is a risk of autoimmunity, infusion reactions, and malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders in patients who receive treatment.
He said Lemtrada was the first drug that was tested head-to-head with interferon beta-1a, which is the standard treatment. In the two trials that were done, he said it was clear Lemtrada was much more effective than interferon beta-1a.
“The longer it goes, the better it looks because you’re changing the immune system with Lemtrada,” he said.
Hunter added that Lemtrada is good in the short term and even better in the long term for relapsing-remitting MS.
“This is a big stick for treating relapsing MS,” he said. “It has a little more risk than other treatments, but you get something for it that any internist could manage.”
This includes monthly laboratory testing for kidney problems at the manufacturer’s expense to watch for blood, thyroid, or kidney problems.
Hunter conducted a phase I non-randomised open label study of 60 patients, using them as their own control. Most patients who switched to Lemtrada had been on the injectable drugs interferon beta-1a or Copaxone.
He said most patients stayed stable for up to two years after one treatment and then got even better with more treatments. “It’s clear Lemtrada works for a while, then it wears off and then we retreat those patients,” he said.
“MRI is really boring after treatment because it stays calm,” Hunter added. “At the same time, some will also get worse. You just have to find the treatment responders.”
Source: MD All Specialities Copyright MD Magazine 2006-2015 Intellisphere, LLC (01/06/15)
Successful relapse management of multiple sclerosis requires a multidisciplinary team that is involved during the multiple stages of patient care, according to a presentation at the Consortium of Multiple Sclerosis Centers Annual Meeting.
“MS care takes a team-based approach,” said presenter Colleen Harris, MN, NP, MSCN, of the University of Calgary Multiple Sclerosis Clinic, Calgary, Alberta, Canada, in an interview with Neurology Advisor.
“Often it may be a nurse at the frontline recognizing some symptoms suggestive of a relapse. Then it is confirmed by either a [nurse practitioner] or neurologist in the field of MS. And if there is significant functional impact, we rely on our rehab colleagues to assist us in full recovery.”
In all, she said the MS team includes neurologists, nurses, support staff, urologists, neuropsychologists, speech therapists, physical, recreational and occupational therapists, social workers/counsellors, ancillary services; and the National Multiple Sclerosis Society/Multiple Sclerosis Association of America.
During her presentation, Harris also defined an MS relapse, which she said is new symptoms of neurological dysfunction or worsening of symptoms that have been stable for the last 30 days of acute or subacute onset and lasting more than 24 hours.
Although there has not been much change over the years with regard to relapse treatment, she said what has changed is the meaning of relapse.
“Now, it means that we are not treating patients with therapies that should reduce and, in many cases, eliminate relapses,” she said, stressing that symptom change may not mean a relapse. “If a neurology practice doesn't see a lot of MS patients, they may misinterpret symptom change as a relapse. If symptom change doesn't meet the definition [for relapse], we have to look for a systemic infection. The most common culprit is urinary tract infection.”
Currently, despite the availability of good treatments for MS, Harris said patients with the condition still do have relapses, which is a signal that their disease is active and that they are not being treated appropriately. “Some of [the relapses] can be quite incapacitating, depending on the location of the relapse and how it impacts the patient functionally,” she said.
When it looks like a patient is having a relapse, the first step is to correctly identify it as a relapse, ruling out any other contributing factors, such as systemic infection or a complication resulting from one of the treatments.
“We look at MS relapses differently now that we have treatments to control them. Corticosteroids and [adrenocorticotropic hormone therapy] are still the mainstay of treatment for relapses,” Harris said. “But appropriate relapse recognition is paramount. If individuals do relapse, they need the treatment and … if they're significantly functionally impaired, they will need to see a rehab specialist.”
Source: Neurology Advisor © 2015 Haymarket Media, Inc (01/06/15)