Results from clinical trials and research in progressive MS, myelin repair, lifestyle and wellness strategies were among more than 3,000 presentations made at MSParis2017, the world’s largest MS research conference, which was jointly organized by the European and Americas Committee for Treatment and Research in MS (ECTRIMS/ACTRIMS). More than 10,000 scientists, clinicians and industry representatives from around the world gathered in Paris during the last week of October to share their research progress.
Advances were reported from many different avenues of research, driving breakthroughs that will stop MS, restore function and end MS forever. Below are a few highlights of presentations. In many cases, studies presented are considered preliminary until they are published in peer-reviewed journals.
Changes ahead for MS clinical practice:
Two previews were provided for soon-to-be published reports that will changed the way doctors diagnose and treat MS.
- Conference participants got an early peak at a revised protocol (“McDonald Criteria”) for diagnosing MS, which may improve the speed and accuracy of diagnosis. More information will be forthcoming after the report is published in a medical journal, said Dr. Jeffery Cohen (Cleveland Clinic), who chaired the international committee that revised the criteria. This effort was led and funded in part by the National MS Society.
- The American Academy of Neurology has been developing guidelines on the appropriate use of MS disease-modifying therapies, to help physicians and people with MS make treatment decisions. The process used to develop the guidelines, which are expected to be published soon, were presented by Dr. A. D. Rae-Grant (Cleveland Clinic).
Stopping MS – Progressive MS
There’s been a rapidly evolving focus of the research community on understanding progressive MS and finding ways to stop it and reverse the damage. This is likely due in part to the activities of the International Progressive MS Alliance
, the first global MS research initiative focused on progressive MS.
For the second year in a row, Alliance activities were the focus of a scientific session at this meeting. This time the leaders of the three Collaborative Research Networks
funded by the Alliance shared an update on their projects with all attendees at the conference. They were also involved in a Webinar held during the meeting, which can be viewed here
Emerging therapy for progressive MS:
Dr. Robert Fox (Cleveland Clinic) presented top-line results from a clinical trial of ibudilast in people with primary progressive or secondary progressive MS. This is an oral compound that is used in Japan to treat asthma and post-stroke dizziness. It’s being tested to see if it can protect the nervous system from MS damage. In this phase 2 trial involving 255 people, which was supported in part by the National MS Society, ibudilast was found to slow the rate of brain atrophy (shrinkage) by 48% compared to a placebo. Finding a way to slow brain atrophy, which has been linked to cognitive and physical disability in MS, may significantly slow disease progression. The main side effects were nausea and skin rash. Larger trials will be needed to better understand the benefits and risks of ibudilast. (Abstract 278
Siponimod MRI results:
Several therapies similar to fingolimod are under development in hopes of reducing the potential for adverse effects. It was previously announced that one of these, called siponimod, could slow progression of disability in secondary progressive MS. This week additional details from the phase 3 trial suggested that siponimod reduced MRI-detected disease activity and brain atrophy, and the benefits were detected as early as week 12. (Abstract 129
Blood marker indicates slowing of damage?
Being able to quickly measure the response to an experimental treatment using a biomarker would accelerate the development of new therapies for MS. Many presentations focused on the presence of fragments of nerve fibers called neurofilament light chains in the spinal fluid or in the blood. Growing evidence suggests these fragments indicate ongoing nerve damage, and if they are reduced, that might indicate a slowing or stopping of the damage. Further verification of neurofilament light as a biomarker of treatment response could improve clinical trials and clinical care for people with MS. (Abstracts 102
Stopping MS – Emerging and Available Therapies
Many presentations showed results from emerging therapies or continued benefits of available therapies, and longer-term safety information and data showing that early and ongoing treatment with a disease-modifying therapy has long-term benefits for controlling disease activity, delaying buildup of disabilities, and protecting quality of life.
Treating pediatric MS:
In the largest clinical trial yet in children and adolescents with MS, oral fingolimod (Gilenya®) reduced the annual number of relapses by 82% over two years, compared to treatment with interferon beta-1a (Avonex®) After two years, 86% of those on fingolimod had not experienced a relapse, compared to 39% of the Avonex group. The trial also showed benefits measured by MRI. Side effects were similar to what have been seen in the adult population. This therapy isn’t currently approved for the treatment of pediatric MS, but the company, Novartis, has announced plans to analyze these data and present the results to regulatory authorities. (Abstract 276
More results from ocrelizumab trial:
Dr. Laura Balcer (New York University) presented additional results from the phase 3 trial of ocrelizumab in relapsing MS showing that the treatment improved vision, especially in those who had visual impairment at the outset of the trial (Abstract 192
Delaying secondary progressive MS:
A large-scale patient registry called MSBase, involving records of thousands of people with MS around the world, allows researchers to ask questions in real-world conditions. Dr. J William L Brown (University of Cambridge, UK) presented results that early treatment with a disease-modifying therapy delays the transition to secondary progressive MS. (Abstract 128
Interferons improve life expectancy:
A study by Drs. Helen Tremlett, Elaine Kingwell and others used administrative health records of over 7,000 people in Canada and France to explore the relationship between the use of interferon beta to treat MS and survival. In this National MS Society-funded study, they found that people who were treated with interferon for three or more years had lower risks of mortality than those who were not. More details will be available when this study is published. (Abstract 218
Phase 3 results for ozanimod:
Results were presented from two phase 3 trials of ozanimod, which is similar to fingolimod, in relapsing MS. Both trials suggested that ozanimod significantly reduced relapse rates compared to people on Avonex® over two years and showed benefits on MRI-detected disease activity. Although there was no evidence that ozanimod slowed the progression of disability compared to those on Avonex, both groups had low rates of progression, making it difficult to see an effect. Phase 3 trials are the final step before a company can apply for approval from regulators like the FDA. (Abstracts 232
Progress in gut microbiome research:
Stopping MS & Restoring Function: Lifestyle Factors/Wellness
A “hot topic” session and several presentations focused on growing information about how gut bacteria influence immune activity. An award-winning presentation by Dr. Alexander Duscha (Ruhr-University Bochum, Germany) described an attempt to translate lab mouse findings into a treatment strategy for people with MS. In mice, one byproduct of gut bacteria called proprionate has been shown to increase a type of immune cell (Treg) that quiets immune attacks. Dr. Duscha and colleagues gave proprionate orally twice a day to 90 people with MS who were on various disease-modifying therapies, and 30 people without MS. The treatment appeared to increase Treg numbers and function and to normalize aspects of the gut microbiome. Additional research may indicate that proprionate could be used as an add-on to ongoing therapy to help restore normal immune function. (Abstract 72
Dr. Ilana Katz Sand and colleagues (Icahn School of Medicine at Mount Sinai, New York) presented initial findings of a long-term study that will track people with early MS over the long term to identify risk and protective factors that may impact a person’s disease course. In a study of the first 105 people enrolled, they found that imaging (MRI) measures of disease activity were related to general health and wellness factors, like sleep, cholesterol levels, and heart rate. This is just the beginning, but the data suggest that paying attention to wellness and health factors – living well with MS
– may play some role in stopping disability progression. (Abstract #P1001
Diet changes metabolism:
The question of whether there is a specific diet that can reduce disease activity is being explored in several ongoing studies. Dr. Kathryn Fitzgerald (Johns Hopkins University, Baltimore) and team presented results from a pilot study of calorie restriction diets involving 36 people. After 8 weeks, the team saw significant changes not only in weight loss, but also in different molecules related to how our bodies process foods (metabolism). These molecules have relevance to immune and nervous system function. The investigators are pursuing these studies with funding from the National MS Society, and will study effects on gut bacteria as well. (Abstract P1244
Stretching improved leg spasticity:
Although there are few studies focusing on benefits of stretching for spasticity in MS, many people are sent to a physical therapist and taught to stretch to treat it. Cinda Hugos (Oregon Health & Science University) and team piloted a program involving home stretching for one month involving 40 people with MS who have leg spasticity (severe muscle tightness). The team found that those involved in the stretching program reported improvement in terms of daily symptoms and activities, compared to people who received standard care. A larger follow up study is planned. (Abstract P899
Another lifestyle factor: Smoking:
A past NIH-funded clinical trial called CombiRx is still yielding important information. More than 800 participants filled out smoking surveys at the start of the study, and researchers looked for any links between smoking status and MS disease activity. Dr. Stacey Cofield (University of Alabama, Birmingham) reported that current smokers were more likely to experience relapses and disease progression than those who never smoked or who quit. (Abstract P410
Restoring Function: Nervous System Repair
Efforts to repair myelin, the nerve insulation that is damaged by MS, are gaining more momentum. There is also emerging information about how the brain repairs itself, and there might be things we can do to encourage that natural repair. An entire “Hot Topics” session focused on how brain activity might influence brain repair and rewiring.
Stimulating nerves to improve myelin repair:
After a nerve wire (axon) is stripped of myelin during MS, there’s a chance that immature myelin-making cells (oligodendrocytes) in the brain will repair it. Now investigators are finding that these cells are more likely to rebuild myelin on axons that show electrical activity. Dr. Maria Angulo (Ecole des Neurosciences, Paris) described studies in which they used a mouse model to stimulate bare axons, and found that this led to better myelin repair. (Abstract 157
Dr. Letizia Leocani (San Raffaele Scientific Institute, Milan) discussed brain-stimulating approaches like repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), which have been used to treat symptoms like depression and pain. But it’s possible that combining those type of external stimulators with things like brain exercises and rehabilitation may help rewire the brain and improve function. (Abstract 159
Factors that control myelin repair:
Dr. Violetta Zujovic (INSERM, Paris) explained that it is still not clear why some people’s brains successfully repair myelin damaged by MS while others experience progressive unrepaired damage and resulting disability. Immune cells play a key role. Her team took immune cells from people with MS and explored their ability to coordinate myelin repair in mice. Ultimately, they expect this research to identify factors from immune cells that could be harnessed as potential treatments to stimulate myelin repair. (Abstract 140
Exercise changes the brain:
Dr. J.-P. Stellmann (Universitätsklinikum Hamburg-Eppendorfm, Germany) and collaborators in France and Germany looked at whether an individualized, supervised aerobic exercise program would improve “functional connectivity” – the connections between different areas of the brain that help the brain to function optimally. In this study of 57 people with relapsing-remitting MS, those who completed the exercise program showed improved fitness as well as improved connectivity after three months, particularly in “hub” regions. Much like airport “hubs” increase connections between areas of the world, hub regions of the brain are vital to integrating information within the brain. (Abstract 234
Ending MS Forever
Although progress has been made in identifying biological pathways that contribute to MS risk, the cause is still unknown. Preventing MS for future generations requires a deep understanding of what triggers MS, how triggers lead to the disease, and how to protect against it. Both genetic and environmental risk factors have been implicated for increasing MS risk – but many people have MS risk factors who will never develop MS, and many people who develop MS may not have been exposed to risk factors identified so far.
MS on the rise?
Eating fish protective?
- Dr. Takashi Yamamura described an increasing incidence of MS in Japan that is not likely explained by better medical facilities or awareness of the disease. His team’s research suggests that previously identified risk factors such as smoking, lower exposure to sunlight or Epstein-Barr virus could not be blamed for the increase. Rather, they suggest that the westernization of the Japanese diet and the resulting changes in gut microbiome may account for the increase of MS in Japan. (Abstract 48)
- And in the U. S., preliminary results from leading experts estimate that nearly 1 million people are living with MS. This is more than twice the previously reported number, which was a result of a 1975 national study and subsequent updates. Dr. Mitchell Wallin presented a poster describing methods used for the estimate. An important next step in confirming this prevalence number includes anticipated publication in a prominent medical journal, expected in 2018. (Abstract P344) Read more in a news bulletin
Dr. Annette M. Langer-Gould (Kaiser-Permanante Southern California) reported on her team’s study examining links between eating fish and the risk of MS using data and survey responses from more than 500 people with MS or CIS (pre-definite diagnosis) and over 600 people without MS. They found that eating fresh fish (not canned or dried) one to three times per month or more often was linked to lower risk of developing MS, and that this was independent of people’s serum vitamin D levels. (Abstract P489
Avonex is a registered trademark of Biogen
Gilenya is a registered trademark of Novartis AG