Myelin Repair, Gut Bacteria, and When Does MS Begin?

At last week’s American Academy of Neurology’s Annual Meeting in Philadelphia, I was struck by the tremendous progress we’ve made in understanding and treating MS. We are closer now than we have ever been to ending MS forever. I’m sharing some of that progress here, and I invite readers to browse the scientific summaries (abstracts) for yourselves, and also check out my colleague’s blog from the AAN, "Explorations of Progressive MS Reported at AAN 2019."

Myelin Repair Trials: I was excited to see first results from a small, open label trial of a thyroid hormone mimic called liothyronine to see if it is safe and holds promise for promoting repair of nerve-insulating myelin, a main target of damage in MS. The study was led by Dr. Scott Newsome of Johns Hopkins University, who received a grant from the National MS Society to support this trial. He reported that it was generally well tolerated, with GI symptoms being the main side effect. This kind of small study isn’t designed to detect actual myelin repair, but the Hopkins team is now analyzing other outcomes to see whether they see hints that a phase 2 trial is warranted (abstract S56.003).

I also learned that two new phase 2 trials are expected to get underway to test the experimental therapy called elezanumab, which in lab models was able to promote repair of axons and myelin,and protect against damage. Results from a phase 1 trial were originally reported last fall at the ECTRIMS meeting. Elezanumab inhibits a molecule that plays a role in stopping the outgrowth of nerve endings during development. Typical for a phase 1 study, it was primarily focused on establishing safety. One of the planned phase 2 trials of this experimental therapy will involve people with progressive MS, and one will involve people with relapsing MS. Exciting news! (abstract S56.001).

Gut Bacteria: There were several presentations focusing on how the microbes that live in our intestines can control immune responses, and looking into differences between people with MS compared to people who don’t have MS. In her talk about gut bacteria and pediatric MS, Dr. Helen Tremlett of the University of British Columbia noted that only half of our body’s cells are human—the rest are microbes, and most of them reside in the gut.
Studies of gut bacteria—collectively called the microbiome—are getting very sophisticated. A team led by Dr. Phil De Jager of Columbia University looked at links between diet, gut microbiome and other factors in 93 people who have no symptoms, but who have close family members with MS. This team previously developed a “risk score” by weighing a person’s known risk factors (such as number of MS-related risk genes and environmental exposures like smoking). Participants gave stool samples and completed surveys about their diets. Among the team’s findings, participants who had the highest risk scores appeared to have fewer bacteria that produce short-chain fatty acids, which have been linked to calmer immune systems and may be protective against immune-mediated diseases. This is just one example of an unfolding story that may lead to approaches for stopping or preventing MS (abstract P4.2-056).
When Does MS Begin? This is a question that received a lot of attention at this year’s AAN, and I think it’s very pertinent to finding a cure. If you ask a person living with MS when their MS began, they may recall a long-ago unexplained symptom, like blurred vision or numbness, that went away after a couple of days. Last year Canadian researchers reported that people with MS went to the doctor or hospital for specific complaints more often than the general population during the five years leading up to their first symptom of MS. This suggests that underlying activity may be underway much earlier than when the first noticeable symptom occurs (read more about this study).

I bring this up because at the AAN this week, there were several presentations about a phenomenon called RIS – short for “Radiologically Isolated Syndrome.” A lot of smart people are collaborating internationally to take advantage of an accidental finding: namely, some people who get brain or spinal cord MRIs for any number of medical reasons are found to have MS-looking lesions on their scans. They don’t have any outward symptoms of MS, they don’t meet the definition of MS, but researchers tracking them have reported that over 5 years, about a third of them are likely to develop definite MS (RIS studies include abstract S37.008 and abstract S37.003).

What researchers are trying to do is figure out if there are very specific MRI or other markers that will identify the one-third who will eventually get MS so that they can intervene early and reduce or prevent damaging disease activity. And that also means finding ways to identify the two-thirds that won’t get MS so that they are not subjected to unnecessary medications.

Finding predictive biomarkers was a big theme at the AAN, and I believe we’ll continue to see a lot of progress in this area, not only for predicting who will get MS, but also predicting who will have mild or aggressive disease, and who will do best with which therapy.

Read more details about AAN 2019 on our website.
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Bruce Bebo, PhD

Bruce Bebo, PhD, is Executive Vice President, Research at the National MS Society, and was previously a research immunologist focusing on the influence of sex hormones on MS. He is a driven and passionate Society volunteer, successful fundraiser and advocate, fueled in part by the fact that his mother had MS.