Presents

DAILY DIGEST

REPORTING FROM ACTRIMS

Americas Committee for Treatment and Research in Multiple Sclerosis
West Palm Beach, Florida

FRIDAY, FEBRUARY 28

Does Key to Severe Multiple Sclerosis Lie in the Genes?

ACTRIMS Forum Keynote Speaker Peter Calabresi Presents New Evidence and Possible Treatment Pathways

At the 2020 ACTRIMS Forum, keynote speaker Peter Calabresi, MD, of Johns Hopkins University presented genetic evidence that may explain severe presentations of MS, and discussed the latest research on remyelination in MS.WEST PALM BEACH, FL — One of the prevailing mysteries of multiple sclerosis (MS) is its variable presentation. Why do some patients with MS have a relatively mild course, and others experience severe disease with more rapid disability progression? At the 2020 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, keynote speaker Peter Calabresi, MD, offered evidence that genetic variants responsible for regulating essential proteins in the immune system may determine severity of MS.

Dr. Calabresi, Professor of Neurology and Director of Neuroimmunology at Johns Hopkins Medicine in Baltimore, MD, opened the ACTRIMS Forum program on Thursday, February 27, with a keynote address dedicated to the memory of Kenneth P. Johnson, MD, one of the founders of ACTRIMS. "Why is this disease so variable? How do we predict which patients may  need a wheelchair in 5 or 10 years and which ones will present with a more benign form of the disease?" There are probably environmental factors at play, Dr. Calabresi suggested, including presence of toxins, dietary factors, and comorbid illnesses such as metabolic dysfunction.

Newer research findings suggest that susceptibility to severe MS may have a genetic component as well. Dr. Calabresi's research team and others have identified links between severe MS and mutations in genes C3 and C1q, essential players in the protein complement system. The complement system is a cascade of plasma proteins that direct antibodies and other immune cells to activate inflammation and clear damaged cells from an organism. Damage to the complement system may be a key to MS severity, and this discovery may lead to newer pathways of treatment.

Oligodendrocytes are generators of myelin in the central nervous system, but inflammation of their precursor cells appears to limit remyelination in people with MS.Patricia K. Coyle, MDAnother compelling question is why attempts at promoting remyelination in MS have been unsuccessful to date. Remyelination of nerve cells is a normal function of the healthy brain, while demyelination is a hallmark of MS pathophysiology. Recent interest has focused on the role of oligodendrocyte precursor cells (OPCs), Dr. Calabresi said. Oligodendrocytes are glial cells essential in the production of myelin, but inflammation inhibits the ability of OPCs to mature into oligodendrocytes. "Suppressing this inflammation may offer a novel approach to treatment that directly address mechanisms of brain injury involved in MS." Dr. Calabresi suggested.

The latest research into the mechanisms of progressive MS is also focusing on other types of glial cells, including astrocytes and microglia. "I think the real key to unlocking progressive MS is going to be in understanding the conversion of glia from a homeostatic or normally functioning state, to a neurotoxic state," Dr. Calabresi predicted.

This year's ACTRIMS Forum gathered over 1,000 researchers and clinicians to share insights into the latest developments in MS research. The 2020 theme "Networks in MS," spans concepts of molecular, cellular, and social networks and focuses on using technology to help expand communication and collaboration between different branches of MS clinical care and research.

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By Katherine Wandersee, for the Consortium of Multiple Sclerosis Centers (CMSC)

© 2020, Consortium of Multiple Sclerosis Centers. Published by Delaware Media Group, LLC. All rights reserved. None of the contents may be reproduced in any form without prior written permission from the publisher. The opinions expressed in this publication are those of the presenters and do not necessarily reflect the opinions or recommendations of their affiliated institutions, the publisher, or Bristol-Myers Squibb.

Oligodendrocytes are generators of myelin in the central nervous system, but inflammation of their precursor cells appears to limit remyelination in people with MS.Patricia K. Coyle, MDAnother compelling question is why attempts at promoting remyelination in MS have been unsuccessful to date. Remyelination of nerve cells is a normal function of the healthy brain, while demyelination is a hallmark of MS pathophysiology. Recent interest has focused on the role of oligodendrocyte precursor cells (OPCs), Dr. Calabresi said. Oligodendrocytes are glial cells essential in the production of myelin, but inflammation inhibits the ability of OPCs to mature into oligodendrocytes. "Suppressing this inflammation may offer a novel approach to treatment that directly address mechanisms of brain injury involved in MS." Dr. Calabresi suggested.

Patricia K. Coyle, MD

Patricia K. Coyle, MD

Patricia K. Coyle, MD

Patricia K. Coyle, MD

Patricia K. Coyle, MD