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Archive for the tag “Studies”

New Research on Lemtrada Reveals Insights into the Cause of Potential Side Effects

Researchers in the U.K. have evaluated additional findings about the immune-system impacts of Lemtrada® (alemtuzimab, Sanofi Genzyme), a disease-modifying therapy for treating people with relapsing MS.

The team used data from phase 3 clinical trials submitted to the European Medicines Agency during the drug’s successful approval process. Some of this data was previously reported at medical meetings and in Lemtrada’s prescribing information.

Among their findings, they report that Lemtrada caused long-term reduction of specific immune cells (memory B and T cells, including regulatory T cells). They also found that the body rapidly repopulated an overabundance of immature B cells.

They propose that the blockade of memory B and T cells drives the beneficial effects of Lemtrada.

They also speculate that the known potential side effect for autoimmune thyroid disease and other autoimmune disorders may be triggered by the overabundance of immature B cells that occurs when there are few regulatory T cells to keep them in check.

Studies like this one, which reveal more information about a therapy’s mode of action, are important and may also lead to insights about how to reduce side effects.

Drs. Klaus Schmierer, David Baker and others at the Queen Mary University of London report their findings in JAMA Neurology, published online June 12, 2017.

Read the open-access paper in JAMA Neurology
Read about Lemtrada
Read more about treating MS

Lemtrada is a registered trademark of Sanofi Genzyme

Dawson’s Fingers ???

“Dawson’s fingers” is the name for the lesions around the ventricle-based brain veins of patients with multiple sclerosis. The condition is thought to be the result of inflammation or mechanical damage by blood pressure around long axis of medular veins.

Dawson’s fingers spread along, and from, large periventricular collecting veins, and are attributed to perivenular inflammation.

Lesions far away from these veins are known as Steiner’s splashes.

Sometimes experimental autoimmune encephalomyelitis has been triggered in humans by accident or medical mistake. The damage in these cases fulfils all the pathological diagnostic criteria of MS and can therefore be classified as MS in its own right. The lesions were classified as pattern II in the Lucchinetti system. This case of human EAE also showed Dawson fingers.

New MS Research

This month in Lancet Neurology, a Canadian research team reports there is a pre-clinical phase in MS. The study used health administration records from four Canadian provinces (British Columbia, Saskatchewan, Manitoba, and Nova Scotia). Due to the nature of the Canadian health-care system, these provinces have computerized health-care records on >99% of residents, including hospital discharges, physician billing, prescription on records, and dates of all medical visits – all records can be linked by a unique health-care number assigned to individuals. Using these records, medical histories for 14,428 MS cases and 72,059 controls were included for this study. They compared health-care utilization in the same five-year period prior MS diagnosis between cases and temporally matched controls.

Interestingly, five years before a MS diagnosis, the number of hospital admissions for people who eventually developed MS was 26% higher than controls, and this increased to 78% higher a year before MS diagnosis. A similar pattern was observed for physician billing (5 years before diagnosis: 24% higher in people with MS than controls; 1 year before diagnosis: 88% higher in people with MS than controls). There was also a substantial increase in the number of prescribed drug classes in people with MS compared to controls (5 years before diagnosis: 23% higher; 1 year before diagnosis: 49%  higher). These results clearly demonstrate a pre-clinical stage for MS where subtle symptoms exist before clinically definitive symptoms (also known as a prodromal stage). With further research, we can explore these subtle symptoms and hopefully diagnose MS earlier and initiate therapeutics earlier, slowing the rate of progression of MS.

From: When do MS symptoms start? By Farren Briggs PhD, ScM; The Accelerated Care Project for Multiple Sclerosis

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)

Study Finds That Some Family Members of People with MS Show Possible Early Signs of the Disease without Symptoms

Summary

  • As part of a large-scale “Genes & Environment in MS” (GEMS) study to understand factors that lead to the development of multiple sclerosis, researchers analyzed the genes and backgrounds of individuals who had no symptoms of MS, but who had close family members with MS.
  • Based on that analysis, researchers identified a group of 40 women at higher risk for developing MS, and 25 women at lower risk. Extensive neurological testing and MRI scanning uncovered possible neurological abnormalities in the higher risk group, and MRI abnormalities in a small proportion of both groups.
  • “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation,” explains co-author Dr. Phillip De Jager. “Family members should be reassured that the vast majority of family members will not develop MS.”
  • The team (including Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).
  • This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Background: An individual’s risk of developing MS increases if a close family member has MS. There is currently no way to predict which family members will develop MS. The goal of the Genes & Environment in MS (GEMS) study is to identify the genetic, environmental and immune profiles that may increase a person’s risk of developing MS.  Researchers are recruiting 5,000 subjects who have at least one first-degree relative with a diagnosis of MS. The GEMS Study is gathering genetic material (DNA) and environmental exposure history from participants as well as blood samples and brain magnetic resonance imaging (MRI) as an option. Investigators are classifying participants using the Genetic and Environmental Risk Score for MS Susceptibility (GERSMS), an experimental approach which incorporates genetic information and environmental exposures to identify people at higher or lower risk of developing MS.

The Study: As part of this large-scale, ongoing study, researchers looked at 65 women who are first-degree relatives of people with MS. The GERSMS indicated that 40 of these women were at higher risk of developing MS, and 25 women were at lower risk of developing MS. These women underwent a comprehensive neurologic examination and MRI scans.

Women in the higher risk group had less than normal vibration sensitivity in their big toes, a finding that indicates potential nerve dysfunction. A small percentage of the women in both groups had more MRI abnormalities associated with MS than one would expect to find in the general population.

The team (Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, Boston, MA, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).

This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Next Steps:  In this study, women at high risk for MS showed possible early manifestations of the disease. “The goal of the Genes & Environment Study is to understand the sequence of events that leads someone to develop MS,” explains co-author Dr. De Jager. “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation. Family members should be reassured that the vast majority of family members will not develop MS.” He notes that the study did not test the possibility of preventive strategies, such as vitamin D supplementation.  “Taking vitamin D is good for bone health, and MS family members should discuss taking such supplements with their physician.”

Read more about research to find the genetic and environmental underpinnings of MS

 

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)

Studies Uncover Possible New Factors That Alter a Person’s Risk for Developing MS

Two recent studies have uncovered new lifestyle factors that may influence whether a person develops multiple sclerosis or not:

Harvard researchers — including National MS Society-funded Dr. Cassandra Munger — reported that children whose mothers were deficient in vitamin D during pregnancy may have nearly twice the risk of developing MS. Additional research is needed to confirm and understand this finding.

On the flip side, researchers at the Karolinska Institute in Sweden and Johns Hopkins University reported that people who drank about four cups of coffee daily had a lower risk of developing MS compared to those who did not drink coffee. Further research is needed to understand this link.

MORE: Research on risk factors is complicated, and cause and effect are difficult to establish. It’s important to note that not every mother with low levels of vitamin D will have a child who develops MS, and not everyone who drinks large amounts of coffee will avoid developing MS.

Read more about risk factors for MS

The Latest on Stem Cell Treatment

Recent media reports have featured news about a clinical trial involving harvesting a person’s own stem cells to treat aggressive multiple sclerosis.
• This treatment, called autologous haematopoietic stem cell transplant (HSCT), attempts to “reboot” the immune system, which is believed to launch attacks on the brain and spinal cord in people with MS.
• HSCT is under investigation in clinical trials in Canada, the United States, Europe and elsewhere. Clinical trials are needed to fully understand the benefits and risks of HSCT in MS, and who might benefit most from this approach, since it does not seem to be effective in all types of MS.
• In HSCT, stem cells from a person’s own bone marrow or blood are stored, and the rest of the individual’s immune cells are depleted usually by chemotherapy. Then the stored stem cells are reintroduced and over time they produce new cells that repopulate the body with immune cells.
• There is exciting progress being made through innovative research related to the potential of many types of stem cells both for slowing MS disease activity and for repairing damage to the nervous system.
• At present, there are no approved stem cell therapies for MS. Stem cell therapy is in the experimental stage, and it’s important for people to have the best available information to understand this exciting area of research and make decisions related to this complex issue.
• In November 2015, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis, bringing leading researchers and clinicians together to confer 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. A summary and consensus on next steps will be published by the conference organizers, with recommendations to help speed the development of new cell-based treatment solutions.
• With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, we believe that the potential of all types of cell therapies must be explored. The Society is currently supporting 12 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 68 stem cell studies over the past 10 years.

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