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ACTRIMS Forum: MS Research Updates on the microbiome, diet, brain networks, and new frontiers

March 6, 2020

This year’s meeting of the Americas Committee for the Treatment and Research of MS (ACTRIMS Forum) was held at the end of February in West Palm Beach, Florida. Here are a few highlights – follow the links provided below to read the scientific summaries (abstracts). Anyone can access all of the scientific abstracts, including nearly 320 posters, presented at ACTRIMS Forum 2020 here.
The theme of ACTRIMS Forum this year was Networks. As explained by
co-chair Dr. Tanuja Chitnis (Brigham and Women’s Hospital), this encompasses many aspects of MS research, such as immune cell networks, the gut microbiome, brain connections, and even the social networks of people with MS. She pointed out research suggesting that people with MS do better when they maintain networks of friends and family.
Dr. Peter Calabresi (Johns Hopkins University) gave the Kenneth Johnson Lecture, describing promising areas of research, including new understanding about the balance between protective and damaging functions of certain cells in the brain. He described the role of the “complement system,” an immune pathway involved in fighting infections, and the formation of nerve connections – synapses – and how this process is disrupted in MS.
Dr. Francisco Quintana (Brigham and Women’s Hospital) received the Barancik Prize for Innovation in MS Research and gave a talk about his work that is beginning to uncover pathways that may help explain how the gut microbiome, the environment, the immune system and the brain interact to cause MS disease activity. These interactions are uncovering possible approaches to stop the disease.
Depression can make MS worse: During her Society-funded Sylvia Lawry Fellowship at Cleveland Clinic, Dr. Jenny Feng examined clinical and imaging data from 2,427 people with relapsing MS who are enrolled in a real-world registry (MS-PATHS). Depression is common in MS, and more prevalent in people with relapsing MS than those with progressive forms. Over 12 months, people with depression showed more worsening in functions, relapses, and disease activity on MRI scans, compared with people who did not have depression. The results suggest that depression is not just a reaction to the stress of MS, but is tied to the disease process itself, and that people should be screened and treated for depression to possibly slow worsening. (Abstract)

Cutting-Edge Technologies: Dr. Sergio Baranzini (University of California, San Francisco) noted an “explosion” of network science, which enables the analysis of very large amounts of data by high-powered computers. The results may reveal new insights and patterns – like zooming out from a close-up a photo to reveal that the pixels make up patterns to create a face. He is working with others on a project called SPOKE, compiling many points of data – such as gene studies, symptoms, medications, lab tests, and others, from 1 million people to begin creating individual and compiled profiles of different diseases. In the future this approach might contribute to personalized medicine – finding the best treatment approach for one individual – and may also reveal clues to what’s going wrong in MS. (Abstract)
The Role of Epigenetics: Many factors combine to make people susceptible to MS. Besides genes, there is the environment, but how can something in the environment change MS risk? Dr. Maja Jagodic (Karolinska Institute) described the field of “epigenetics,” which she described as basically the way DNA is packaged and used within cells. The environment changes this packaging, and those changes can influence MS risk and also disease course, suggested Dr. Jagodic. There is also some promising evidence that some epigenetic changes may be reversible.  (Abstract)
Dr. Patrizia Casaccia (City University of New York) further explored studies of epigenetics in cells from people with MS. She showed that disease-modifying therapies could cause positive changes to one type of epigenetic mechanism known as “DNA methylation.” In another study, obesity was shown to cause negative changes to DNA methylation, causing increased numbers of immune cells that were linked to brain volume loss and worsening disease. Obesity in adolescence has been identified as a factor that can increase the risk of getting MS; this study adds to evidence that it may also impact the disease course in adults. (Abstract) Epigenetics is a fast-growing field that has potential to increase our understanding of MS and also holds potential for new therapies.
The topic of gut microbiome is becoming more popular, not just in MS but other disorders, as results come in on the influence that the friendly and unfriendly bacteria and other “bugs” that reside in the intestines have on the brain, immune cells and MS disease activity. A whole session and several posters were devoted to this important topic.
Dr. Jennifer Gommerman (University of Toronto) provided a closer look at the gut microbiome, noting that there’s just a thin separation between the bacteria inside the intestines and the immune cells that surround them. She discussed studies showing that immune cells that are involved in MS-like disease (EAE) are influenced by the microbiome, and those cells can move to the brain to either ramp up inflammation or ramp it down. Studies have shown that transplanting feces from people with MS into germ-free mice made EAE more severe, compared to transplants from people without MS. Likewise, fecal transplants from people with secondary progressive MS aged 50 or older made EAE worse. One explanation is the fact that as people age, their microbiome becomes less diverse, which might not be good. (Abstract)
Dr. Howard Weiner (Brigham and Women’s Hospital), who was one of the earlier explorers of gut microbiome in MS, described recent attempts to apply what’s been learned to develop therapies. In a small probiotic approach, they gave a supplement of Lactobacillus, Bufidobacterium, and Streptococcus to 9 people with MS and to a group of people without MS. They found that over two months that the probiotic appeared to be anti-inflammatory. He said that now his team is working on a probiotic customized to treat MS, that would include potentially beneficial bacteria. His team is planning a pilot study of fecal transplant in progressive MS. They are also synthesizing by-products related to microbiome that may ultimately be used as another treatment approach.
Dr. Weiner noted that some studies have identified an overabundance of Akkermansia as being negatively linked to MS, but further studies have suggested that the increase of this bacteria may be the body’s way to turn off inflammation. So if some species are elevated in MS, it doesn’t necessarily mean they are harmful, and if some species are reduced in MS, it doesn’t mean that they should be increased. This points to the fact that “we’re not ready yet” to prescribe a particular way to improve outcomes by altering the gut microbiota in MS, he said. (Abstract)
Dr. Emmanuelle Waubant (University of California, San Francisco) and collaborators in the U.S. Pediatric MS Centers reported today that an abundance of bacteria in two orders, Pasteurellales and Enterobacteriales, were linked with reduced risk of later relapse in children and teens with MS. The team is now analyzing any links to MRI-detected disease activity. More research by this team and others will help determine whether altering the quantities of normal gut bacteria may impact disease in both children and adults with MS. This study was supported by the NIH and the National MS Society (Poster P187)
Dr. Ellen Mowry (Johns Hopkins University), who has been studying the role of diet in MS for several years, reviewed what’s known about how diet may impact MS risk, the disease course, and the microbiome, and some dietary approaches that are being tested as strategies to address symptoms and wellness in MS. She noted that obesity can increase a person’s odds of getting MS, and also can worsen the course of MS. One reason, Dr. Mowry explained, is that fatty tissue promotes inflammation.
What about diet and disease course? She noted that many diets have been proposed and are under way, including paleo, gluten free, Swank, low-fat plant diet, fasting-style diets, Mediterranean diet. Dr. Mowry’s team conducted the ATAC-MS Study, which compared calorie restriction to intermittent fasting in 36 people with MS, who were provided food to ensure compliance over the 8 weeks of the trial. Generally they did OK on the diet, they lost weight, participants had more diverse microbiomes, and there was less depression. But when they were asked to continue on their own after the study period, participants found it hard to keep up.
Dr. Mowry discussed how difficult it is to design and conduct diet studies, and that after what’s been learned so far, it may be more feasible to encourage people to improve their healthy eating, in a way that is sustainable as a lifestyle. She is leading the Charms Research Study (Characterizing Healthy Actions Relevant to MS) looking at the influence of a range of lifestyle characteristics, including diet, on disease course. So far, higher-quality diets are linked to better walking ability and other measures, but this study is still underway.
Asked what she advises her clients, Dr. Mowry suggested that it’s not certain that any particular diet will make their MS better, but given the evidence around obesity, she suggests a healthier diet, such as a Mediterranean-style diet, that keeps a person’s body weight to within normal range, appears to be beneficial.  (Abstract)      Read more about diet and MS
Telehealth to increase social networks: Since research has shown that people with stronger social networks do better coping with their MS, Dr. Victoria Leavitt and colleagues at Columbia University developed and tested two telehealth programs. One is an online support group to reduce loneliness; the other is an online partnering to encourage physical activity and increase accountability. Both programs were beneficial; the support group reducing loneliness, and the pasrtnering program increased physical activity. These results add to others suggesting the value of telehealth programs to increase access to programs that can improve quality of life for people with MS. (Poster P068)
Some people on oral therapies aren’t getting their lab tests: Dr. Helen Tremlett (University of British Columbia) and collaborators looked at health data related to people who were prescribed oral therapies that require regular blood and urine tests to ensure safety. The team found that most people got the tests before beginning the therapies, but then many didn’t keep up with the tests. These results should be a wake-up call to prescribers and to those taking the therapies, since the lab tests are often the first indicators that the therapy is causing adverse effects. (Poster P104)
Light Therapy for Fatigue: Student Andre Vogel and colleagues (Massachusetts General Hospital) did a pilot study to test the feasibility of using bright white light to treat MS fatigue, since it has been shown helpful treating fatigue in other disorders. They divided a group of people with MS who had fatigue into two groups: half received bright white-light boxes and half received red dim light boxes as a control. Both groups used the boxes at home for one hour, two times per day for four weeks. Although this pilot study wasn’t designed to detect effectiveness, both groups reported benefits, suggesting a strong placebo effect. They plan to use their results to design a larger, longer study of bright white light therapy to treat MS fatigue. (Poster P293)
Toward making MRIs more standard: The Consortium of MS Centers convened experts to make recommendations for how brain and spinal cord MRIs should be done so that these become part of the standard of care for people with MS. Adoption of these standards, which have been harmonized with those recommended by the European group, MAGNIMS, would improve the types of information that can be gathered from MRIs to improve care. The group has plans for publishing and widely disseminating these standards. (Poster LB310)
Synapses are junctions where one nerve cell communicates with another nerve cell. Dr. Dorothy Schafer (University of Massachusetts) noted growing evidence that synapses are damaged when the brain is undergoing inflammation in MS, and experimental ways her team and others are testing to protect synapses from loss. One prime candidate for mediating this loss is an immune system protein known as complement component 3. The goal is to figure out how to turn off the activity of complement 3 without interfering with its role in fighting infections. (Abstract)
Role of Microglia: Microglia are immune cells that reside in the brain and spinal cord. They have many beneficial and detrimental roles, especially in progressive MS. Dr. Martin Kerschensteiner (Ludwig Maximilians University of Munich) commented that microglia are also participants in synapse loss in MS, responding to signals that drive them to clear away the synapses. He discussed the possibility of protecting synapses by reducing the activation of microglia. (Abstract)
Role of Astrocytes: The most abundant cells in the brain are called astrocytes, and they also appear in MS lesions, explained Dr. Veronique Miron (University of Edinburgh). There is a growing appreciation that they perform many diverse functions that can be damaging or beneficial. She showed evidence that astrocytes play an important role in myelin repair by becoming activated and supplying a needed myelin component, cholesterol, to the cells that make myelin. There is a molecular switch (NRF2) that controls this participation in repair, she noted, and it needs to be considered in strategies to repair myelin in MS. (Abstract)
Other talks in the brain connections session focused on ways to use imaging methods like MRI and PET (positron emission tomography) to visualize brain and spinal cord cells, tissues, nerve connections, MS lesions, and to detect myelin repair, which is becoming so important as more and more clinical trials testing repair strategies get underway.

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Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. There is currently no cure for MS. Symptoms vary from person to person and range from numbness and tingling, to mobility challenges, blindness and paralysis. An estimated 1 million people live with MS in the United States. Most people are diagnosed between the ages of 20 and 50, and it affects women three times more than men.

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