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Archive for the tag “research studies”

Researchers Recruiting African Americans with MS Across the U.S. for Genetics Studies – Key to finding cause of MS and better treatments

Rationale: Genes are known to play a role in determining who is susceptible to developing multiple sclerosis, and may also influence the course of the disease. People living with MS can make a difference in studies searching for these genes by donating their DNA from blood samples. Identifying the exact location of MS genes could help determine who is at risk for developing the disease and may provide clues to its cause, prevention, and better treatment. Focusing on ethnic groups with lower susceptibility to MS (such as African-Americans) and higher susceptibility (such as individuals of Northern European descent), and searching for what is common and what is different in their genes may help pinpoint regions that contain MS genes. Large numbers of participants are needed to accelerate this research.

Details: It is not necessary to travel to San Francisco to participate in this study. Once an individual has completed the initial online intake form and has agreed to participate, they are emailed the links to two additional online forms and sent a kit via express mail. The kit includes a consent form, a health information privacy form, and a medical records release form. The kit also includes everything necessary for the blood draw, which can be taken to your local Quest Diagnostics Lab, where the blood can be drawn and then returned in a prepaid envelope to the UCSF MS Genetics Lab. There is no cost to the study participants.

Contact: To participate or request additional information, please complete our brief intake survey.

OR you may contact us directly:

Clinical Research Coordinator
UCSF Multiple Sclerosis Genetic Susceptibility Project
675 Nelson Rising Lane, Suite 235A, Box 3206
San Francisco, CA 94158
Email: msdb@ucsf.edu
Website: http://msgenetics.ucsf.edu/index.html
Toll Free Phone: 1-866-MS-Genes (1-866-674-3637)

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New Study: Resilience in People with Chronic Disease is Linked to Social Satisfaction and Quality of Life – Not Physical Function

Summary

  • A survey of more than 1500 people with MS and other chronic diseases shows that resilience (the ability to solve problems and bounce back from difficult situations) is linked to satisfaction with social roles (such as work and family responsibilities) and quality of life, but not to physical function.
  • Understanding factors that promote resilience may help people with MS to not only cope with unpredictable changes in health and abilities, but to thrive in spite of these changes.  Learn more about how the resilience factor can help you to thrive. Watch an education program on Resilience: Addressing the Challenges of MS.
  • The team (Samuel Battalio, BS, and colleagues at the University of Washington) has published results in Archives of Physical Medicine and Rehabilitation (2016 Dec 16).

Background: Research on psychosocial issues forms a cornerstone of finding life-changing solutions for people with MS. MS can have a significant impact on a person’s emotions, not only because MS is unpredictable and challenging to live with, but because it affects parts of the brain that control mood. This study specifically looked at factors that can affect resilience (i.e., the ability tackle problems, find solutions and bounce back from difficult situations).

The Study: The team reviewed information on 1574 people with MS, muscular dystrophy, post poliomyelitis syndrome, and spinal cord injury, which was gathered from an ongoing survey that is tracking people in the United States who are aging with physical disabilities. Information was collected on resilience using a clinical scale, and on other factors (including physical function, satisfaction with social roles – meaning work and family responsibilities, and quality of life) using questionnaires that assess how people report their own health status.

The results suggest that people who reported significantly greater satisfaction with social roles and significantly greater quality of life had significantly higher resilience. This relationship was slightly different between men and women, in that men who expressed greater levels of satisfaction with social roles reported higher levels of resilience. Surprisingly, noted the authors, resilience was not significantly greater in people who reported better physical function.

The team (Samuel Battalio, BS, and colleagues at the University of Washington) has published results in Archives of Physical Medicine and Rehabilitation (2016 Dec 16).

Next Steps: The authors note that resilience is complex, and that further research could help uncover particular aspects of resilience that may be most beneficial to individuals.  Understanding factors that promote resilience may help people with MS to not only cope with unpredictable changes in health and abilities, but to thrive in spite of these changes.

There are behaviors that can help promote individuals’ resilience:

World’s Largest MS Research Conference Highlights Advances in Progressive MS, Gut Microbiome, Managing Symptoms, and New Approaches to Restoring Function

Results from clinical trials, including new approaches to treating progressive MS, lifestyle and wellness research and myelin repair strategies were among more than 2,000 presentations made at the European Committee for Treatment and Research in MS (ECTRIMS) meeting held in London, England in September.
The world’s largest gathering of MS researchers convened more than 9,000 scientists and clinicians and industry representatives from across the globe, including many National MS Society-funded researchers, meeting and presenting on cutting-edge MS research progress. In addition, the European Rehabilitation in MS network met jointly with ECTRIMS this year.

During the conference, the International Progressive MS Alliance announced new investments of over $14 million US dollars to support three Collaborative Network Awards. These international teams were selected to accelerate the pace of research in key areas to speed new therapies for progressive MS.

Below are highlights of presentations focused on stopping MS, restoring function, and ending MS forever. In most cases, studies presented are considered preliminary. Many will be analyzed more thoroughly, and likely published in peer-reviewed journals.

STOPPING MS

Many presentations showed continued benefits of available therapies and longer-term safety information, as well as more evidence that early and ongoing treatment with a disease-modifying therapy has long-term benefits for controlling disease activity, delaying accumulation of disability, and protecting quality of life.

Siponimod in secondary progressive MS: More details were presented from a 60-month, phase 3 clinical trial of the experimental oral therapy siponimod (Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS. The trial met its primary endpoint, with those on active treatment showing a modest 21% reduced risk of disability progression compared to those on placebo. Secondary endpoints suggested that those on active therapy had 23.4% lower average change in brain volume and reduced MRI-detected lesion volume. The medication showed a similar safety profile to others that work by preventing white blood cells from entering the central nervous system. (Abstract #250)

More details from trial of lipoic acid in secondary progressive MS: Dr. Rebecca Spain and colleagues (Oregon Health & Science University) presented results from a small, controlled clinical trial on the oral anti-oxidant supplement called lipoic acid in people with secondary progressive MS. The lipoic acid group had 66% less brain tissue shrinkage, or atrophy, than the group taking inactive placebo pills. This pilot study suggests potential benefits if they hold up in a larger trial. (Abstract #222)

New results on gut bacteria: Efforts are advancing to pinpoint bacteria in the gut that may drive inflammatory immune system activity in MS and others that can suppress it, which may open the door to novel probiotic or other therapeutic approaches to treating MS.

  • Drs. Yan Wang, Lloyd Kasper and colleagues (Dartmouth Medical School and Eastern Washington University) reported that treating mice with the gut-related molecule called polysaccharide A (PSA) expanded a type of immune cells called “Regulatory B cells” (Bregs) which promote an immune response that prevents mice from getting MS-like disease. (Abstract #181) Members of this team also reported that PSA had positive effects in mice with progressive MS-like disease. (Abstract #P465)
  • Dr. Sergio Baranzini (University of California, San Francisco) and other collaborators in the National MS Society-supported MS Microbiome Consortium are analyzing gut bacteria to unearth clues about MS susceptibility and progression. They analyzed bacteria in stool samples from 64 people with MS who had received treatment for MS, and 68 people without MS. Certain bacteria were increased in people with MS, and those bacteria increased immune cells (T helper 1 cells) that are major players in MS immune attacks. Another type of bacteria that could suppress the immune attack was reduced. (Abstract #179)

Disappointing results for nerve-protection approaches: A small two-year clinical trial of fluoxetine (same compound as the anti-depressant Prozac) did not meet its goal of improving walking speed in people with progressive MS. The multi-center team from Belgium is still analyzing other results, such as changes in MRI and cognition. (Abstract #253) Likewise, a trial conducted at the University of Oxford tested the ability of amiloride to protect against nerve damage in people with acute optic neuritis (often an early sign of MS) failed to show any neuroprotective benefit. (Abstract #102) Additional trials of neuroprotective approaches to MS are ongoing.

Vitamin D deficiency and smoking linked to progression: Dr. Maria Isabel Zuluaga and team (Vall d’Hebron University, Barcelona) explored the independent impacts of smoking and vitamin D deficiency in a large group of people followed over time. They found that those with severe vitamin D deficiency (defined as blood levels at less than 8 ng/ml) showed an increased risk for MS disability, and active smokers also had an increased risk for disability progression. (Abstract #252) Graduate student Ms. Eva Rosa Petersen (Danish MS Center, Copenhagen) also found that smoking intensity was linked with higher frequency of relapses among people taking interferon beta. Smoking one pack of cigarettes per day increased relapse rates by 25%. (Abstract #178)

Vitamin D added to Rebif: A large international trial did not show a statistical difference between treatment groups after adding vitamin D (14,000 IU [350 µg] vitamin D3 daily) or placebo to Rebif therapy in relapsing MS, in terms of the percent of participants who were free from disease activity after 48 weeks. Dr. Raymond Hupperts (Orbis Medical Centre, Sittard-Geleen, The Netherlands), who presented results, noted that both groups were stable, which likely contributed to the inconclusive results. (Abstract #166)

Biomarkers under development: Teams are making headway toward having a simple test that can predict a person’s disease course, progression and response to therapy. Dr. Bibiana Bielekova (National Institute of Neurological Diseases and Stroke) and team examined proteins in the spinal fluid of people with neurological diseases, including all types of MS, and identified a “signature” of markers that distinguished MS from other diseases, and also differentiated relapsing MS from progressive MS. (Abstract #219). Other investigators also reported progress in this area, including advances using “neurofilament light chain” as a biomarker. (Such as Abstracts #183, #249) These early results need further development but indicate that  sensitive biomarkers for predicting disease course and response to therapy may become useful tools for the clinical management of MS.

RESTORING FUNCTION – WELLNESS, LIFESTYLE, SYMPTOMS

Home-based rehabilitation can work: With funding from the National MS Society, Dr. Gabriel Pardo (Oklahoma Medical Research Foundation) and colleagues compared the benefits of three approaches to rehabilitation for gait and balance in a small study: unsupervised home-based exercise 5 times/week; home-based exercise supervised remotely by a physical therapist 2-3 times per week via audio and visual conferencing; and home-based exercise plus in-person physical therapy 2-3 times/week. They found that all participants improved, and that the telerehabilitation program worked as well as the onsite program to improve gait and balance. Further research in larger trials could make telerehabilitation a cost-effective and more accessible alternative for people with MS. (Abstract #120)

Tackling fatigue: Dr. Vincent de Groot (VU University Medical Center, Amsterdam) reported results from three clinical trials testing different strategies over 16 weeks to lessen fatigue, in 90 people with MS: aerobic training, cognitive behavioral therapy, and energy conservation management. Only cognitive behavioral therapy effectively reduced severe fatigue in this short-term study. This is a commonly available type of psychotherapy. (Abstract #142) Read more about managing fatigue

Pain more common than previously reported: Dr. Carolyn Young (University of Liverpool) and colleagues found that nearly 66% of over 700 people with MS reported nerve pain. Higher levels were found in those who had MS for a longer time, had more severe disability, or were not working. (Abstract #P337Read more about addressing pain in MS

New trial confirms Ampyra (fampridine) benefits: Dr. Jeremy Hobart (Plymouth Hospitals NHS Trust) presented results from a large clinical trial of fampridine, a twice-a-day oral therapy that was previously approved for its ability to improve walking.. This trial wanted to show evidence that its benefits include meaningful functional improvements for people. The results over 6 months showed that 43% of those on active therapy had significantly better self-reported walking ability, mobility, and balance than those on placebo, with no new safety issues reported. (Abstract #254)

Cognitive rehabilitation enhances brain connections: Several studies showed that rehabilitation to improve cognition goes hand-in-hand with changes in brain connectivity (how areas of the brain interact). While many of these treatments are still experimental, some are available from rehabilitation specialists such as speech pathologists or neuropsychologists. Discuss options with your MS doctor:

  • Dr. Brian Sandroff (Kessler Foundation, West Orange, NJ) and colleagues showed that treadmill training improved information processing speed and brain connectivity in a small pilot study funded by the Society. (Abstract #P796)
  • Dr. Pietro Iaffaldano (University of Bari, Italy) and colleagues showed that a home-based computerized training program that targeted specific cognitive issues improved overall cognitive function significantly more than a non-specific program. Also, those who had less function in certain brain areas showed greater improvement after cognitive training. (Abstract #145)
  • Oiane Rilo (University of Deusto, Bilbao, Spain) and colleagues showed that a three-month, group-based cognitive rehabilitation program improved working memory, information processing speed, verbal memory and executive function (which is important in problem solving and planning), and altered brain connectivity. (Abstract #144)

Emerging treatment for muscle spasticity: Dr. Daniel Kantor (Kantor Neurology, Ponte Vedra Beach, FL) and colleagues report that in a trial of 354 people with relapsing-remitting or secondary progressive MS, Arbaclofen Extended Release Tablets (Osmotica Pharmaceuticals) significantly reduced spasticity compared to baclofen. The extended-release tablets caused significantly less sleepiness, drowsiness and dizziness than baclofen. (Abstract #128) The company reports that it has filed for FDA approval of Arbaclofen.

RESTORING FUNCTION – NERVOUS SYSTEM REPAIR

More Anti-LINGO Results: In June 2016 Biogen announced that its phase 2 clinical trial of anti-LINGO (proposed name opicinumab), an approach to repair myelin, did not meet its primary endpoint of improvement in physical function, cognitive function, or disability. The trial involved 418 people with relapsing MS who were taking interferon beta-1a (Avonex) plus one of several doses of intravenous opicinumab or placebo for 72 weeks. Dr. Diego Cadavid from the company described ongoing evaluations from the extensive testing and monitoring during the trial, which are helping to pinpoint the patient population, dosage and outcome measures that would inform the design of any future trials of anti-LINGO.  (Abstract #192)

Myelin repair in pediatric and adult MS: Dr. Sabine Pfeifenbring (University of Göttingen, Germany) and an international team analyzed brain biopsies from children who had been diagnosed with MS and compared the extent of damage and natural myelin repair against those of adults with MS. They found that children showed less damage to myelin-making cells and more evidence of myelin repair than adults. However, some myelin repair was found to occur at virtually all ages in MS. (Abstract #194)

Exercise enhances myelin repair in mice: To investigate some reasons why exercise promotes benefits in people with MS, Drs. S. Jensen and Wee Yong (University of Calgary) did a study where mice with myelin damage in their spinal cords used running wheels soon after the injury. They reported finding more evidence of generation of myelin-making cells and myelin repair in the active mice than those that did not use the running wheels after injury. (Abstract: #P1210)

Emerging approaches to protection and repair:  Dr. Martin Sanders (Io therapeutics) presented results from mice suggesting that the compound IRX4204 promotes repair of damaged myelin in mice. He noted that previous studies suggested that IRX4204 also showed signs of reducing immune attacks and protecting against nerve loss. This work was supported in part by a National MS Society’s Fast Forward investment. (Abstract #193)

Drs. Sarah Starossom, Samia Khoury and team (Brigham and Women’s Hospital, Boston) reported on studies of Chi3l3, a naturally occurring molecule in the brain that can stimulate the transformation of resident stem cells into myelin-making cells. The team noted that it plays an important role in recovery from the MS-like disease in mice, and may have potential for development as a new treatment approach in MS. (Abstract #195)

Positive Results Announced from Clinical Trial of BAF-312 (Siponimod) in Secondary Progressive MS

Summary

Results presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) provided additional details from a 60-month, phase III clinical trial of the experimental oral therapy siponimod (BAF312, Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS.

The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression compared to those on placebo. Secondary endpoints suggested that those on active therapy had 23.4% lower average change in brain volume and reduced lesion volume.

The therapy was generally well tolerated and similar to adverse events reported for similar compounds.

Details

Background: Siponimod (BAF312) is an experimental immune system-modulating therapy that was designed to be a more selective sphingosine 1-phosphate receptor modulator than Gilenya® (fingolimod, Novartis International AG). Gilenya, was approved in 2010 for adults with relapsing forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability. Siponimod previously demonstrated safety and efficacy on MRI scans in a phase II study in people with relapsing-remitting MS (The Lancet Neurology, 2013 Aug;12(8):756-67).  Siponimod is thought to act by retaining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and from entering the central nervous system. Siponimod also distributes effectively to the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory or other effects.

The Study: Participants were randomly assigned to take siponimod or placebo capsules daily for up to 60 months. The primary endpoint of the study was reducing the risk of disability progression, as measured by the EDSS scale at three months. Secondary endpoints included reducing the risk of disability progression as measured by the EDSS at six months versus placebo, the risk of worsening mobility as measured by the timed 25-foot walk test, disease activity as observed on MRI scans, relapse rate, and safety/ tolerability.

Results:  Results were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on September 17, 2016. The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression (confirmed at 3 months) compared to those on placebo. Secondary endpoints suggested that those on active therapy had at 26% reduced risk of disability progression (confirmed at 6 months), a 23.4% lower average change in brain volume, and reduced MRI-detected brain lesion volume. There was no significant difference seen between groups in the timed 25-foot walk. Relapse rates were significantly lower in those taking siponimod.

Safety: The therapy was generally well tolerated and similar to adverse events reported for similar compounds. Serious adverse events occurred in 16.7% of participants. The serious adverse events reported to be more likely for those taking siponimod included nervous system disorders and infections.

Comment:
“These results suggest a modest benefit for people with secondary progressive MS, which is a positive step forward in the global effort to speed solutions for people living with this chronic form of the disease,” said Timothy Coetzee, PhD, Chief Advocacy, Services and Research Officer at the National MS Society. “We look forward to learning additional details about its potential benefit and safety.”

Study suggests antibody may have therapeutic effect on MS

Researchers have developed an antibody with potential therapeutic effects against multiple sclerosis. The discovery opens up a new strategy for controlling the disease.

For the cells of the immune system circulating in the bloodstream to reach the central nervous system, they must penetrate the blood-brain barrier and blood-spinal cord barrier. During previous work, the authors studied a factor involved in opening the blood-brain barrier, the NMDA receptor. They found that blocking the interaction of this receptor with tPA has beneficial effects linked with maintaining the integrity of the barrier.

Scientists at the Institut National de la Santé et de la Recherche Médicale, in France, developed a monoclonal antibody (Glunomab) directed against the specific site on the NMDA receptor to which tPA binds. In cellular models of the human blood-brain and blood-spinal cord barriers, the use of this antibody prevented opening of the barrier under inflammatory conditions, limiting the entry of lymphocytes. The team then tested the therapeutic effects of the antibody in an experimental mouse model of MS. After intravenous injection of Glunomab, the progression of partial or total paralysis of the limbs – as assessed by a clinical score – was blocked. In these treated mice, this effect was linked with reduced infiltration of lymphocytes into the nervous tissue, and reduced demyelination.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the authors argue that by preventing myelin destruction by the cells of the immune system, this strategy might represent a promising therapy for the control of MS.

The study was published in the journal Brain.

Study Shows Expansion of Stem Cell Clinics in the U.S. and the Need for Better Oversight

Researchers have published a paper describing the proliferation of stem cell clinics in the United States and ethical issues and regulatory concerns that come with marketing unproven treatments for many conditions. Their study shows that many different types of unproven stem cell treatments are being offered, and highlights concerns for the safety of people who undergo these treatments.

There is exciting progress being made through innovative research related to the potential of many types of stem cells for slowing MS disease activity and for repairing damage to the nervous system. At present, there are no approved stem cell therapies for MS. People need the best available information to understand this exciting area of research and make decisions related to this complex issue.

The paper’s findings support the need for stem cell therapy to be explored in the context of carefully conducted clinical trials that can determine what the optimal cells, delivery methods, safety and actual effectiveness of cell therapies might be for people with MS.

Positive Results from Study of Bone Marrow-Derived Stem Cells in People with Aggressive, Relapsing MS

Summary

  • Researchers in Canada have published results of a long-term trial of an individuals’ own (autologous) hematopoietic (blood cell-producing) stem cell transplantation. The study involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies.
  • Three years after the procedure, 70% remained free of disease activity, with no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression.
  • None of the surviving participants, who were followed for 4 to 13 years after the procedure, experienced clinical relapses or required MS disease-modifying therapies to control their disease, and 40% experienced reductions in disability.
  • One of the participants died and another required intensive hospital care for liver complications. All participants developed fevers, which were frequently associated with infections, and other toxicities.
  • Additional research is focusing on figuring out who might benefit from this procedure and how to reduce its risks.

“These results suggest that aggressive MS may be stopped with an effective but risky procedure, for a subset of people,” said Dr. Bruce Bebo, Executive Vice President, Research, at the National MS Society. “Additional research by investigators around the world is focusing on figuring out who might benefit from this procedure and how to reduce its risks, which can include death.”

Details
Background: An experimental procedure that has been explored for several years in MS is called “autologous hematopoietic (blood cell-producing) stem cell transplantation” – or HSCT. This procedure has been used in attempts to “reboot” the immune system, which launches attacks on the brain and spinal cord in people with MS.

In HSCT, the stem cells (derived from a person’s own bone marrow or blood) are stored, and the rest of the individual’s immune cells are depleted by chemotherapy. Then the stored stem cells are reintroduced by infusion into the vein. The new stem cells migrate to the bone marrow and over time produce new blood cells, including immune cells. The goal of this currently experimental procedure is to establish a new immune system that no longer recognizes myelin and other nervous system tissue as dangerous. In theory, this should stop the attacks that lead to tissue damage and disability.

There are a number of laboratories around the world testing variations of HSCT for the treatment of autoimmune diseases, including MS. Preliminary findings suggest this is a promising, but potentially risky strategy for the treatment of MS.

The Study: Drs. Harold Atkins, Mark Freedman and team at the Ottawa Hospital, University of Ottawa and other institutions in Canada conducted a Phase 2 trial of HSCT that involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies. No control group was used which would have enabled comparison against the results found in the treatment group. The procedure used by this group included complete destruction of bone marrow cells and an additional step that enriched the transplanted cells for stem cells.

Results – Safety: One of the participants died of transplantation-related complications that caused liver failure and another required intensive hospital care for liver complications. The treatment regimen was modified over the course of the study to reduce toxicity, but all participants still developed fevers, which were frequently associated with infections.

Results – Effectiveness: Three years after the procedure, 70% of the participants remained free of disease activity, meaning they had no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression. The remaining 30% experienced progression of disability. In addition, for the entire follow-up period ranging from 4 to 13 years after the procedure, of the 23 survivors:

  • None experienced clinical relapse, had new active inflammatory MRI brain lesions, or required MS disease-modifying therapies to control their disease.
  • The average rate of brain atrophy (shrinkage), a measure that has been linked to MS progression, returned to levels associated with normal aging.
  • 40 percent experienced some lasting reversal of disability such as vision loss, muscle weakness and balance problems.
  • Some were able to return to work or school.

The results were published online on June 9, 2016 in The Lancet.  Major funding for the study came from the MS Society of Canada and its affiliated Multiple Sclerosis Scientific Research Foundation.

Next Steps: Rigorous clinical trials of stem cell therapies are needed to determine their safety and effectiveness in people with MS. Trials of this and other stem cell therapy approaches are taking place in Canada, the United States, Europe and elsewhere. To help explore the potential of stem cell therapy, in November 2015, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened in Lisbon, Portugal under the auspices of the International Advisory Committee on Clinical Trials in MS (a group jointly sponsored by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis). Seventy leading researchers and clinicians conferred on clinical trials needed to provide answers about which types of cells, which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS. Read more about this meeting

Read more about stem cells and MS

Canadian Researchers Uncover Rare Gene that Increases Risk of Progressive MS

Researchers at the University of British Columbia have uncovered a rare gene mutation that appears to dramatically increase the risk, in some individuals, of developing a severe form of progressive multiple sclerosis. While the cause of MS is not known, scientists believe several different factors, including susceptibility genes, may interact to trigger the disease. The gene was discovered in two unrelated families that had multiple members with MS. The researchers also determined that the gene (NR1H3) contains instructions for a protein called LXRA, which is thought to be a control switch for genes involved in many functions, including some that help control inflammation and integrity of nerve-insulating myelin in the brain and spinal cord. This type of discovery can provide crucial clues to biological pathways that underlie MS, and may lead to new approaches for stopping MS and restoring function. The study, by Drs. Carles Vilariño-Güell, Weihong Song, A. Dessa Sadovnick and others, was funded in part by the MS Society of Canada and appeared in the journal Neuron on June 1, 2016.

German Study Suggests Leukemia and Colorectal Cancer Rates Increased with Mitoxantrone Use for MS

Summary

  • A study of 676 people with MS treated with the MS therapy mitoxantrone in Germany reveals that the rates of acute myeloid leukemia (a type of cancer) and colorectal cancer were significantly increased above what would be expected in the general population there. Rates of other cancers were not increased.
  • The authors note that if the findings are confirmed, recommending colonoscopy after treatment may be advisable, since if found early enough, colorectal cancer is curable.
  • The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Background: Mitoxantrone is a powerful immune-suppressing therapy. Prior to its approval for use in MS, it was used only to treat certain forms of cancer. It acts in MS by suppressing the activity of immune T cells, B cells, and macrophages that are thought to lead the attack on nerve-insulating myelin. The U.S. Food and Drug Administration approved mitoxantrone for reducing neurologic disability and/or the frequency of relapses in people with secondary progressive MS or worsening relapsing-remitting MS. The total lifetime dose is limited to avoid possible heart damage. Acute myeloid leukemia has been previously reported in people treated with mitoxantrone for MS or cancer.

The Study: Investigators identified 677 people with MS seen at the University of Würzburg MS center between January 1994 and December 2007 who had received mitoxantrone. They were able to follow up with 676 of these patients.

The results show that 37 people developed cancer after taking mitoxantrone, including nine cases of breast cancer, seven cases of colorectal cancer, and four cases of acute myeloid leukemia. The rate of acute myeloid leukemia was 10 times that seen in the general population in Germany. The rate of colorectal cancer was three times that seen in the general population in Germany. The rate of breast and other cancers was not increased over that seen in the general population in Germany. Older age at treatment was associated with increased risk of cancer, but not prior use of other immunosuppressive treatments, or duration of treatment with mitoxantrone.

The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Comment: The authors state that if the findings are confirmed, “posttreatment colonoscopy might improve the risk-benefit ratio of this highly active immunosuppressive drug,” since if found early enough, colorectal cancer is curable. They also note that mitoxantrone is currently the only MS therapy approved for treating secondary progressive MS, and that the overall rate of cancers may still justify the use of mitoxantrone in people who are severely affected with MS and where there are no better treatment options available.

Read more about mitoxantrone
Read more about treating secondary progressive MS
Read more about making treatment decisions in MS

 

Antihistamine Shows Evidence of Stimulating Myelin Repair in Small Phase II MS Study – More studies needed before the full benefits and risks of this approach can be verified

Summary

  • In a small, phase II clinical trial, the oral antihistamine clemastine modestly improved the transmission of electrical signals in the optic nerve in participants with MS who had optic nerve damage.
  • The improved transmission indicates that nerve-insulating myelin was repaired along the nerve pathways.
  • Clemastine is an over-the-counter allergy medication. Doses in this trial exceeded the maximum recommended for over-the-counter use. Clemastine affects a range of targets in the body, and involves the risk for side effects, particularly at increased dosages.
  • This team is planning an additional trial to further determine the safety and effectiveness of clemastine, as well as studies to identify compounds that may enhance myelin repair and cause fewer side effects.
  • Clemastine was identified as having possible myelin-repairing properties through innovative preclinical research conducted by National MS Society-funded Jonah Chan, PhD, who went on to become first recipient of the Barancik Prize for Innovation in MS Research for this pioneering work.
  • Preliminary results will be presented by the clinical trial’s lead investigator Ari Green, MD (University of California, San Francisco), at the annual meeting of the American Academy of Neurology being held in Vancouver, Canada, April 15 to 21.

Background: In MS, the immune system attacks and destroys myelin, the fatty substance that surrounds and protects the nerve fibers, and the nerve fibers can also be damaged. Current therapies are largely aimed at dampening the immune attacks. However, a therapy that repairs damage to myelin and nerve fibers is also necessary.
A team at the University of California, San Francisco led by National MS Society-funded Harry Weaver Neuroscience Scholar Jonah Chan, PhD, invented a new micropillar technology to rapidly identify compounds that stimulate the regrowth of myelin. The team initiated a screen using this technology, testing a library of 1000 drugs already approved by the FDA for other conditions for their ability to promote the development of myelin-making cells and wrapping of myelin around the micropillars. Clemastine, an oral antihistamine used to treat allergy symptoms, was identified through this process. Dr. Chan was the first recipient of the Barancik Prize for Innovation in MS Research for this pioneering work.

The Clinical Trial: Ari Green, MD, led the team conducting the clinical trial. They administered oral clemastine or inactive placebo twice daily to 50 people with MS and optic nerve damage for 150 days. For the first three months of the study, people were given either clemastine or a placebo, and for the second two months, those initially given clemastine received the placebo and vice-versa. Tests were performed before and after treatment that measured visual evoked potentials. Visual evoked potentials measure transmission of electric signals along optic nerve pathways in response to stimulation. Delays in this transmission occur when the myelin is damaged and if these delays are reduced, it is an indication that myelin repair is occurring along the nerve pathways. (Participants had significant delays in transmission in at least one eye.)

Delays in visual evoked potential were reduced by 1.9 milliseconds per eye, a statistically significant result. The results hinted at a reduction in vision impairment as well, but it did not reach statistical significance. Fatigue increased mildly in participants taking clemastine.

Clemastine is an over-the-counter allergy medication. Doses in this trial exceeded the maximum recommended for over-the-counter use. Also, clemastine affects a range of targets in the body, and involves the risk for side effects, particularly at increased dosages.

Dr. Green cautions that more research with larger numbers of people is needed before doctors can recommend clemastine as a treatment for people with MS. This team is planning an additional trial to further determine the safety and effectiveness of clemastine, as well as studies to identify compounds that may enhance myelin repair and cause fewer side effects.

Drs. Green and Chan both received Society funding to launch their early careers as independent researchers focused on MS, including Harry Weaver Neuroscience Scholar Awards.

Comment: “This preliminary report is exciting, and we look forward to seeing the full results of this clinical trial of clemastine presented and then published,” says Bruce Bebo, PhD, Executive Vice President, Research at the National MS Society. “Finding a way to repair nervous system damage to restore function to people with MS is a very high research priority.”

The 2016 Annual Meeting of the American Academy of Neurology will take place in Vancouver, BC, Canada, April 15-21. The National MS Society will be providing reports summarizing studies. Anyone can get a preview of the technical summaries, or abstracts, of presentations to be given at the meeting at this link, free of charge. 

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