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Multiple Sclerosis: Paving the Way to a Cure

— Advances in MS are a great success story in modern medicine, says Stephen Hauser, MD

MedpageToday

At the joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), , of the University of California San Francisco, spoke during a plenary session titled, "MS: Pathway to a Cure."

In this exclusive ľֱ video, Hauser gives a synopsis of the first portion of his session, which explained the pathology and underlying mechanisms of multiple sclerosis (MS), and how this knowledge is bringing us closer than ever to a cure.

Following is a transcript of his remarks:

Hello, I'm Steve Hauser from the University of California San Francisco. Delighted to present a synopsis of the seminar that I gave at ECTRIMS 2023 in Milan earlier this month in October 2023.

Without question, advances in MS are one of the two or three greatest success stories in modern medicine. Therapeutics that have been developed over the past generation have been increasingly effective and increasingly safe, especially for the early relapsing inflammatory component of MS. We've also made important inroads into being able to treat the later progressive phase of MS. But this really represents the elephant in the room, how to treat progressive MS more effectively, and can we move from suppressing MS entirely to actually curing the disease? And furthermore, how do we even know when a cure is present?

In other autoimmune diseases, one of the huge advances has been the development of specific biomarkers that are present in the bloodstream. And these are almost always autoantibodies that can detect disease at its very earliest stages, or even more importantly, before the disease begins. Autoantibodies in systemic lupus, in rheumatoid arthritis, and in type 1 diabetes have been incredibly powerful tools to understand the ramp-up to clinical autoimmunity.

And we now understand that most autoimmune diseases can be envisioned as having three phases. The first phase of benign autoimmunity where there is no tissue damage, but clinically important autoantibodies begin to form. The second stage, pathogenic autoimmunity where tissue damage mediated by autoimmune responses begins to happen. And then the third phase when clinical disease begins.

The presence of these autoantibody biomarkers permits us to identify patients at risk for autoimmune diseases before the disease actually begins. And in diseases like rheumatoid arthritis and more recently type 1 diabetes, it has now been possible to conduct clinical trials before the disease can be diagnosed or even begin in order to prevent the disease from occurring -- so primary prevention.

Teplizumab [Tzield], an anti-CD3 monoclonal antibody was recently approved by the Food and Drug Administration for prevention of type 1 diabetes. An amazing advance.

In multiple sclerosis, which as most in the audience knows, is an autoimmune, demyelinating, central nervous system-restricted neurologic disease, we've not had autoantibodies that can be measured in the bloodstream and that are diagnostic of MS, or that appear before the disease begins. We now have such autoantibodies, and part of my talk described the use of the Department of Defense Serum Repository, which is a banked repository now more than 40 years old, which continues to build from more than 10 million servicemen and women, and more than 81 million samples from these 10 million people.

Dipping into the DOD Serum Repository, we were able to select people who were healthy, but who subsequently developed multiple sclerosis, plus matched controls, and identify a highly specific, albeit insensitive, autoantibody that predicted the onset of MS at least 5 years before the disease begins. This autoantibody has a lead proline and then a polyserine and arginine motif that is shared with a number of viral proteins, in particularly the BRRF2 protein of Epstein-Barr virus. And it is likely that an autoimmune response could be triggered through molecular mimicry by an immune response against Epstein-Barr virus.

So this may explain the well-known epidemiologic association of Epstein-Barr virus infection, and especially infectious mono, with the subsequent development of MS. And this autoantibody might mark a very specific immune response that could be cross-reactive and explain why some people infected with Epstein-Barr virus then go on to develop multiple sclerosis.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.