Myelin Repair, Clinical Trials, Gut Bacteria, and Exercise Headline at ECTRIMS2019, the World’s Largest MS Research Meeting
September 23, 2019
Results from clinical trials, research on stem cells, myelin repair, gut bacteria, exercise and other lifestyle interventions were among nearly 1,700 presentations made at the world’s largest MS research conference, organized by the European Committee for Treatment and Research in MS (ECTRIMS). Nearly 10,000 researchers, clinicians and industry representatives from around the world gathered in Stockholm, Sweden in mid-September to share their research progress. Browse presentations, brief summaries (abstracts) and posters, or follow links below to specific studies.Read a blog: Impressions from ECTRIMS2019Listen to conference highlights in a RealTalk MS podcast 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 during conferences like this are considered preliminary until they are published in peer-reviewed journals.
Many presenters shared results demonstrating 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.
MS Diagnosis is Quicker: Dr. Leszek Stawiarz (Karolinska Institutet, Stockholm) and team looked back through decades of health records from the Swedish MS Registry to compare how long it took to diagnose MS using different diagnostic criteria. For example, using the Poser criteria (in use in the 80’s and 90’s), it took on average about 6 years to diagnose MS. Today, using the more modern McDonald criteria, a majority of people were diagnosed within one year. This means that more people are being diagnosed at earlier stages of the disease, which enables earlier treatment and better outcomes for many. (Abstract and Presentation 99)
Imaging to Understand and Diagnose MS: Many presentations focused on advances in imaging technologies to examine characteristics of MS brain or spinal cord lesions (areas of damage or disease activity). For example, Dr. Margareta Clarke (Vall d´Hebron University Hospital, Barcelona) reported that using a widely available 3T MRI scanner, lesions showing the presence of iron rings and lesions that are located around a small vein (called the central vein sign) could be detected in people with MS, but not other neurological diseases. These signals could distinguish people with MS from people with similar diseases. Imaging studies like this will not only lead to better diagnosis, but also offer new insights into what’s causing MS damage. (Abstract and Presentation 108)
Phase 3 Results from Two Experimental Therapies: Results were presented from two recently completed Phase 3 clinical trials testing potential therapies for relapsing forms of MS. Data from these trials will be used to support applications for regulatory approval from the FDA (and regulators in other countries) in the next few months: • Dr. Stephen Hauser (University of California, San Francisco) presented the first detailed results from two parallel Phase 3 trials testing ofatumumab (Novartis) versus oral Aubagio® (teriflunomide, Sanofi Genzyme) in more than 1800 people with relapsing MS. Ofatumumab is self-administered as a monthly under-the-skin injection that depletes immune B cells, an approach similar to Ocrevus®(Genentech). Those on ofatumumab had significant reductions in relapse rates, active MRI-detected lesions, and disability progression compared to those on Aubagio. Injection-site reactions were the most common adverse event. (Abstract and Presentation 336)
• Dr. Ludwig Kappos (University Hospital Basel) presented the first detailed results from a Phase 3 trial testing oral ponesimod (The Janssen Pharmaceutical Companies of Johnson & Johnson) versus oral Aubagio in more than 1100 people with relapsing MS. Ponisimod binds to a docking site (S1P1 receptor) on immune T cells and B cells which causes a reduction in the levels of these cells in the blood, an approach similar to Gilenya® and Mayzent® (Novartis). After two years, those on ponesimod had significant reductions in relapse rates and active MRI lesions, and favorable changes in fatigue symptoms. The most common adverse events were abnormal levels of liver enzymes and a slight increase in seizures. Gradually increasing the dose reduced the incidence of temporary heart symptoms seen with similar therapies. (Abstract and Presentation 93)
Pregnancy and MS Therapies: Figuring out how to plan a family and when to stop and start disease modifying therapy can be a complex decision. Among several studies reported that will help to answer these questions, Dr. Marie D’Hooghe (Vrije Universiteit Brussel, Belgium) cited a recent study indicating that about 10% of women with MS have gotten unexpectedly pregnant while they were taking an MS treatment. Since some disease-modifying therapies may increase the risk of birth defects, awareness of family planning for men and women of reproductive age is important, and their healthcare providers should repeatedly ask them about their plans around having children. (Abstract and Presentation 21)
Gut microbiome: Several presentations focused on the role of intestinal bacteria (gut microbiome) in MS. Previous research has found differences in the gut microbiome between people with MS and people without MS, and that certain gut bacteria may stimulate immune cells to turn off MS-like relapses. Further research should help determine whether probiotic approaches to alter gut bacteria will be an effective strategy in MS: • Dr. Ali Mirza (University of British Columbia, Vancouver) and collaborators surveyed published papers related to the gut microbiome in MS over the last ten years. Results were not always consistent in terms of the types and amounts of bacteria showing differences between people with MS and people without MS. The use of disease-modifying therapies was consistently linked with normalizing the gut microbiome. (Abstract P678)
• To try to control for variations in gut microbiome findings among studies, collaborators in the International MS Microbiome Study (iMSMS) from different cities are collecting stool samples from 2,000 people with MS, paired with 2,000 of their own household members who do not have MS. Dr. Xiaoyuan Zhou (University of California, San Francisco) shared preliminary learnings: there is wide variation in microbiome between cities and individuals. Those from the same household had more similarities than random pairs. This preliminary evaluation will inform the team’s analysis of results when the study is completed. (Abstract and Presentation 223)
RESTORING FUNCTION - MYELIN REPAIR
There is a critical need to find solutions that will reverse the loss of function faced by many people living with MS. One approach is to develop therapies that promote repair of the myelin coating on nerve fibers, which is damaged in MS and can lead to disrupted nerve signaling and nerve loss. There are several clinical trials underway testing myelin repair strategies. Progress in the area of myelin repair was summarized by Dr. Catherine Lubetzki in her Charcot Lecture (Presentation).
Mesenchymal Stem Cell Therapy: Results from two key studies were presented that bring us closer to understanding the potential of individuals’ own mesenchymal stem cells (adult stem cells found in bone marrow, skin, fat and other tissues) to stop inflammation and promote myelin repair in MS: • Dr. Antonio Uccelli (University of Genoa) presented the first results from a multi-center international Phase 2 placebo-controlled trial involving 144 people with relapsing and progressive forms of MS. Individuals’ own bone marrow-derived mesenchymal cells were extracted and multiplied, then re-infused into the vein (IV) two times and evaluated after 24 weeks. The primary endpoint was safety and the number of active (gadolinium-enhancing) lesions. There were no differences in the number of active lesions in those receiving cells versus the control group, and no safety issues. There was a slight reduction in relapse rates that did not reach statistical significance. Additional analyses are ongoing. (Presentation 32 and Poster P1378)
• Dr. Dimitrios Karussis (Hadassah University Hospital, Jerusalem) presented results of his team’s single-center, Phase 2 double-blind trial of individuals’ own bone marrow-derived mesenchymal stem cells in 48 people with active progressive MS. Individuals’ cells were extracted, enhanced in an unspecified way, multiplied and re-introduced either by IV infusion or infusion into the spinal fluid (intrathecal - IT). Result suggest that those who received the cells IT experienced significantly less worsening of disease progression than those on IV or placebo 12 months after treatment. No safety issues were reported, and the investigators believe the results suggest a neuroprotective or reparative outcome, warranting a Phase 3 trail. (Abstract and Presentation 157)
The different outcomes in these trials suggest that the way the cells are treated before administration and the route of delivery may determine the effectiveness of cell-based therapies.
Early Myelin Repair Trial: Dr. Scott Newsome (John Hopkins University, Baltimore) described the first results from a National MS Society-funded Phase 1 trial testing the safety of liothyronine, a treatment for low thyroid function. Thyroid hormones are known to stimulate myelin growth but cannot be tolerated at doses needed to do so. For this open-label study, the team enrolled 20 people with relapsing or progressive MS who were taking a disease-modifying therapy and who had normal thyroid function. They found that it was generally well tolerated and additional analysis of results should determine if it warrants further testing. (Abstract and Presentation 60)
RESTORING FUNCTION – WELLNESS
Emerging evidence is providing insights into how exercise, lifestyle activities, and other health issues may influence MS progression and symptoms. Wellness approaches empower people to do something now that can impact their MS and quality of life.
Exercise in MS: Disease Modifying? In an invited talk, Dr. Ulrik Dalgas (Aarhus University) discussed what is known and not yet known about maximizing benefits of exercise for people with MS. He cited previous studies suggesting that exercise can delay an MS diagnosis, protect brain volume, protect against relapses, and may provide short-term improvements in fatigue, pain, depression, balance, and walking ability. Being fit can help reduce the likelihood of other disorders such as cardiovascular disease, which when layered onto MS can make MS worse. His perspective is that exercise should be treated as a “medicine” to be prescribed as soon as a person is diagnosed with MS. (Presentation 172)
Exercise for Better Sleep? Dr. Alham Al-Sharman (Jordan University of Science and Technology, Irbid) and colleagues performed a small pilot study to see whether six weeks of moderate aerobic exercise could alter sleep quality compared to non-aerobic exercise done at home. The aerobic group showed significant improvement in sleep quality tested with a variety of measures, and those improvements were accompanied by increased blood levels of serotonin, a nerve messenger chemical with many functions that has been linked to mood, sleep and other functions. (Abstract and Poster P712)
Another Reason Not to Smoke: Dr. Ebtesam Alshehri (Cleveland Clinic) reported on the team’s study that linked individuals’ smoking status with results of cognition tests and MRI scans of brain atrophy (shrinkage) in 997 people with MS. After accounting for age and other variables, they found that current smokers scored lower on cognition tests and showed more brain atrophy. Former smokers did a little better on cognition tests, but not as well as people who never smoked. (Abstract P461)
The Fog Lifts: Dr. Anthony Feinstein (University of Toronto) and collaborators compared two groups of people with MS who had cognitive impairment and who had used cannabis at least 4 days per week for many years. One group abstained from cannabis for 28 days and the other group continued using cannabis. After 28 days, those who went off cannabis showed significant improvement in memory, information processing speeds, and executive function compared to those who continued heavy use of cannabis. (Abstract and Poster P542)
One definition of ending MS is preventing anymore new cases from occurring. To do that, we need more information about what triggers MS. There were several sessions and presentations focusing on risk factors such as genes, exposure to viruses, and sunlight/vitamin D and the roles they play in making people susceptible to developing MS.
How Early Does MS Start? Dr. Kjetil Bjornevik (Harvard T.H. Chan School of Public Health, Boston) presented his team’s findings looking at blood (serum) samples from 60 military personnel who went on to develop MS years later. Compared to a control group, those who developed MS showed higher than usual levels of a molecule (neurofilament light chain - NfL) that reflects damage to the nervous system. The levels of sNfL were increased six years before the clinical onset of MS. Other studies have shown that years before they are diagnosed with MS, people show a pattern of doctor visits for specific problems. These studies suggest that MS begins well before there are perceptible signs, offering hope that there will be a way to predict and prevent MS before it becomes full-blown disease. (Abstract and Presentation 284)
Vaccinations Not Linked to MS: Dr. Christiane Gasperi (Technical University of Munich) presented results looking at any link between MS and various vaccinations that occurred within 5 years before the initial diagnosis, using medical claims data for more than 12,000 people with MS compared to more than 79,000 people without MS. They found no link between vaccinations and the development of MS, and in fact they found people who had received vaccinations had a lower risk of being diagnosed within the next five years. (Abstract and Presentation 224)
Is it MS? There’s a rare phenomenon called RIS (radiologically isolated syndrome) where some people who undergo brain MRIs are found to have MS-like lesions without MS symptoms. A global team of collaborators have been tracking these individuals to see which go on to develop MS, and whether there is a way to predict this outcome in advance. Dr. Christin Lebrun-Frénay (Nice Cote d’Azur University) reported on a 10-year follow-up study showing that 51% had converted to MS. Those more likely to convert tended to be younger and to have specific types of brain and spinal cord lesions. Two clinical trials are ongoing to see if conversion to MS can be prevented in people with RIS. (Abstract and Presentation 97)