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Research Update from ACTRIMS Forum: Day 3

March 3, 2020

The third and final day of the Americas Committee for the Treatment
and Research of MS (ACTRIMS Forum) in West Palm Beach, Florida continued the Networks theme, with talks focusing on complex interconnections within the brain and how those connections can be impacted by MS; the connections between the gut bacteria (microbiome) and immune and brain cells; and what’s being learned about diets and MS. (Check out other ACTRIMS topics from Day 1 and Day 2.)
Here are a few highlights – follow the links provided below to read the scientific summaries (abstracts). Access all of the presentations given at ACTRIMS Forum 2020 here.
Synapses are junctions where one nerve cell communicates with another nerve cell.  Synapses were the focus of the day’s first talk by Dr. Dorothy Schafer of the University of Massachusetts. She 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, of the 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 of the University of Edingurgh. 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 myelin repair.
A whole session was devoted to the intestinal bacteria and other microorganisms, collectively called the gut microbiome, and its influence on immune and brain cells. Dr. Helen Tremlett of the University of British Columbia reviewed some of the findings so far. She noted that the microbiome can influence response to therapies, and disease-modifying therapies can influence the makeup of one’s microbiome. Some other things that can alter the gut microbiome include antibiotics, smoking, and diet. In a Society-supported study of kids with MS, presented earlier at ACTRIMS, the microbiome influenced future rate of MS relapses. “There’s a lot we don’t know,” she said, and huge opportunities and challenges to harness the potential of addressing MS at the gut level. (Abstract)
Dr. Jennifer Gommerman of the 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 of 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)
What about diet? Dr. Ellen Mowry of Johns Hopkins University reviewed what’s known about how diet may impact MS risk and disease course, and some dietary approaches that are being tested as strategies to address symptoms and wellness in MS. She mentioned the Ausimmune Study in Australia, which notes that people with healthier diets, as well as those who ate more canned fish, had reduced odds of being diagnosed with MS. Dr. Mowry also 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.
She 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. Dr. Mowry is leading the Charms Research Study (Characterizing Healthy Actions Relevant to MS) at Johns Hopkins that is 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

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