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World’s Largest MS Research Conference: Understanding MS and New Strategies to Restore Function

October 17, 2018


Results from clinical trials and research in myelin repair, gut bacteria and lifestyle influences were among more than 1,700 presentations made at ECTRIMS2018, the world’s largest MS research conference, which was organized by the European Committee for Treatment and Research in MS (ECTRIMS). Over 9,400 researchers, clinicians and industry representatives from around the world gathered in Berlin in mid-October to share their research progress.  
Advances were reported from many different avenues of research, driving breakthroughs to a cure that will stop MS, restore what’s been lost and end MS forever. Below are only a few highlights of many important presentations. Usually studies presented are considered preliminary until they are published in peer-reviewed journals.


Stopping MS

Many presentations showed results suggesting continued benefits of available therapies, and longer-term safety 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. Several studies also reported on efforts to determine how to predict an individual’s disease course and progression to guide better treatment decisions.
 
New approach to B cell therapy? First results were reported by Dr. Xavier Montalban (University of Toronto, Ontario) from a phase 2 trial of evobrutinib – an oral therapy that targets B cells, but with a different mechanism of action than Ocrevus. Evobrutinib inhibits an enzyme called “Bruton’s tyrosine kinase,” reducing the activation of B cells and inhibiting immune cells called microglia, which have been linked to MS progression. In this 24-week study, the drug was fairly well tolerated and reduced the occurrence of active MRI brain lesions.(Abstract 322)
 
Test-driving the new diagnostic criteria: Several presentations reported on differences in applying the updated 2017 McDonald Criteria for the Diagnosis of MS against the previous version. The National MS Society co-sponsored, with ECTRIMS, the committee of experts that developed the updated criteria as well as previous versions. Most studies reported that the updates enabled faster, more accurate diagnoses, enabling earlier treatment more likely to forestall the accumulation of damage.
 
Another benefit of earlier treatment: Dr. A. Kavaliunas (Karolinska Institute, Stockholm) and collaborators compared economic outcomes among people with MS who initiated therapy with a disease-modifying therapy within two years of diagnosis versus those who started therapy later in Sweden, a country with universal healthcare. They reported that those who started treatment later had higher chances of losing earnings/income than those who started earlier, adding economic data to growing health-related evidence that earlier treatment is optimal. (Abstract 145)
 
Disappointing results from progressive MS trial: First results were presented by Dr. Jeremy Chataway (University College London) from “MS-SMART,” an innovative phase 2 clinical trial that compared three potential neuroprotective therapies to determine their ability to slow brain atrophy (shrinkage) in people with secondary progressive MS. A total of 445 people in the UK participated. Although the results confirmed that this multi-arm trial design is feasible and will speed the search for new therapies in the future, in this trial none of the therapies showed the ability to slow down brain shrinkage. While this is disappointing, we often learn as much or more from our failures as we do our successes. A detailed review of the results is likely to yield insights that may identify leads for new progressive MS therapies. The National MS Society was one of many co-funders of this innovative approach to the search for solutions for people with progressive MS. (Read more)
 
Blood marker indicates slowing of MS damage? Being able to quickly measure the response to an experimental treatment using a biomarker would accelerate the development of new therapies for MS, especially progressive MS. Many presentations focused on the presence of fragments of nerve fibers called neurofilament light chains in the spinal fluid or in the blood. These fragments indicate ongoing nerve damage, and if they are reduced, that might indicate a slowing or stopping of the damage. Further verification and standardization of neurofilament light as a biomarker of treatment response could improve clinical trials and clinical care for people with MS. Members of the International Progressive MS Alliance held a meeting during the conference to help coordinate these efforts. (Abstracts 158, 286)
 

Stopping MS/Restoring Function: Lifestyle Factors/Wellness

A growing area of research focuses on how lifestyle factors, wellness and activity can influence a person’s experience with MS. Evidence is also building on the role of gut bacteria in disease activity. Wellness studies suggest that some of these factors are modifiable and addressing them may improve health, quality of life and even disease course.
 
Body mass and brain tissue loss: Dr. Ellen Mowry (Johns Hopkins University, Baltimore) and collaborators used data collected over 5 years to determine whether blood levels of vitamin D or obesity influenced MRI measures of brain degeneration, which is linked to disability progression. In 469 people in the study, the researchers found that higher body mass index, but not vitamin D, was linked to greater declines in brain volume. This study, funded by the National Institutes of Health, raises the question of whether reducing obesity may alter disease course. (Abstract 169) Calculate your BMI
 
Exercise – “Keep going!” Dr. Sadeghi Bahmani (University of Basel, Switzerland) and colleagues conducted a successful 8-week trial of active workouts three times per week, finding that participants had improvement in depression, sleep, fatigue and anxiety. The effects lasted 8 to 12 weeks, but decreased afterward, suggesting the need for continuous exercise for sustained improvements. (Abstract P1274)
 
Mediterranean diet: Dr. Ilana Katz-Sand (Mount Sinai Hospital, New York) and colleagues tested the benefits of the Mediterranean diet (emphasizing plant-based foods like fruit and vegetables). They randomly assigned 36 women with MS to this diet or educational seminars as a control. Those on the diet received training with a nutritionist and attended monthly meetings to promote adherence. Preliminary results showed participants could stick with the diet and showed some improvements in fatigue and quality of life. Larger studies are needed to confirm its benefits. (Abstract P643).
 
Gut bugs and the brain: National MS Society-supported postdoctoral fellow Dr. Anne-Katrin Pröbstel (University of California, San Francisco) and collaborators reported on novel interactions between abnormal gut bacteria and immune activity related to MS, including recruitment of activated immune cells into the brain and spinal cord. This is a novel potential pathway linking the gut microbiome and the immune response in people with MS that could result in new more effective targets for therapy. (Abstract P1760)
 
More reasons to give up smoking: Several studies showed that smoking significantly increased the risk of disability progression and cognitive impairment. Dr. Mar Tintoré (Cemcat-Vall Hebron University Hospital, Barcelona) reported that vitamin D deficiency or smoking significantly increased the risk of progression (Abstract 170). Dr. Marianna Cortese (Harvard T.H. Chan School of Public Health, Boston) reported that smoking or vitamin D deficiency increased the chances of cognitive decline. (Abstract 321) Need help quitting? Visit smokefree.gov or call 800-QUITNOW.
 

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. Several invited lectures focused on next steps and new targets for developing therapies to promote myelin repair, including one by Dr. Catherine Lubetzki (Sorbonne University, Paris – Abstract 326) and Dr. Charles ffrench-Constant (University of Edinburgh – Abstract 215).  
 
First tests in people of antibody for brain repair: Dr. Bruce Cree (University of California, San Francisco) presented results of a phase 1 trial of a monoclonal antibody called elezanumab, which inhibits a molecule that plays a role in stopping the outgrowth of nerve endings during development. In animal models, elezanumab was able to promote repair of axons and myelin, and even protected against damage. The trial involved people with secondary progressive MS and relapsing MS. The results suggest that it was well tolerated, and did not cause flare-ups on MRI scans. Typical for a phase 1 study, it was primarily a safety study. (Abstract P899)
 
Capacity of brain’s stem cells in MS: The lab of Dr. Tanya Kuhlmann (University Hospital Munster, Germany) conducted a series of experiments to see if myelin repair in MS is blocked because people with MS have impaired myelin-making stem cells or some other issue. The team took skin cells and reprogrammed them to become oligodendrocyte precursor cells which would normally conduct myelin repair. They found that the cells could turn into the right cells, migrate and divide like cells from people without MS, but that they were blocked by the inflammatory environment (Abstract 82), suggesting that taming inflammation may promote myelin repair.


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.
 
High salt diet a risk factor? Dr. Ralf Linker (Friedrich-Alexander-University Erlangen-Nuremberg, Germany) gave an invited talk about the possible link between high salt diets and the development of MS and disease activity. There have been mouse studies showing salt can increase disease activity, and other studies in people with mixed results, some supporting the link and others not. He showed studies in mice suggesting that high salt diet depletes gut bacteria in the lactobacillus family, making MS-like disease worse, and that feeding the mice these bacteria as a pro-biotic made the mice better. Further research could lead to tests of probiotics to treat MS. (Read published abstract in Nature)
 

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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