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Pioneering Proposal for a New Framework to Describe Types of MS

November 18, 2022

-- lays groundwork for better understanding and treatments in the future
An international panel of MS experts has published a paper that proposes a new approach to how different types of multiple sclerosis are typically described. The goal is to eventually move away from clinical descriptions of separate phases, like relapsing-remitting, primary progressive, or secondary progressive MS. Instead, the panel proposes understanding MS as a continuous disease process that is influenced and driven by underlying mechanisms of nervous system injury, counter-balanced by how well an individual’s body can repair or compensate for that injury. Ultimately, having a biological understanding of what drives any individual’s disease course will lead to better, more personalized treatments that can stop MS in its tracks. This is a key milestone in Pathways to Cures.
The paper, by Tanja Kuhlmann, MD (University Hospital Münster, Germany) and collaborators, was written on behalf of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, a longstanding effort to provide perspective and guidance related to planning and implementing clinical trials for new treatments for MS.  The Committee is jointly supported by the National MS Society (USA) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
“This proposal is among many initiatives that the Committee has supported over the years as part of its overarching aim to constantly improve, update and enhance clinical trial design and inform clinical care delivery for people living with MS and their healthcare teams,” commented Dr. Ruth Ann Marrie, who chairs the International Advisory Committee on Clinical Trials in MS.
Describing MS based on the underlying biology, rather than only how it appears clinically, will require a better understanding of the mechanisms that drive disease worsening. The paper reviews ongoing research to uncover and detect the underlying biological mechanisms active in individuals with MS and identifies knowledge gaps.
Some key points:
  • Any new framework for classifying MS in the future will require a sea change in how individuals with MS, clinicians, and drug developers and regulators understand and describe MS. This would enable the development and approval of more biologically based treatment approaches for each individual with MS. This will be an international collaborative effort requiring several years to complete.
  • Factors that are likely to influence how any individual experiences MS and its disease course include the person’s duration of disease, age, biological sex, genes, race and ethnicity, other health conditions, health behaviors, therapies, and exposure to social and environmental factors.
  • Some mechanisms being investigated for their role in nervous system injury include acute and chronic inflammation, myelin loss, nerve fiber (axon) and neuron loss, and insufficient energy to maintain the health of brain cells (mitochondrial dysfunction).
  • An ongoing balance between injury and the ability to repair or compensate for that injury is likely to determine what an individual’s MS looks like and evolves throughout its course.
  • This framework for describing MS is the foundation needed to achieve personalized treatment plans for all people living with MS. The next step is to develop the tools to determine an individual’s disease course and make them available to people living with MS and their clinicians to make biologically based (personalized) treatment decisions. 

Multiple sclerosis progression: time for a new mechanism-driven framework,” by Drs. Tanja Kuhlmann, Marcello Moccia, Timothy Coetzee, Jeffrey A. Cohen, Jorge Correale, Jennifer Graves, Ruth Ann Marrie, Xavier Montalban, V. Wee Yong, Alan J. Thompson, Daniel S. Reich, on behalf of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, was published online on November 18, 2022 in Lancet Neurology.

About Multiple Sclerosis

Multiple sclerosis is an unpredictable disease of the central nervous system. Currently there is no cure. Symptoms vary from person to person and may include disabling fatigue, mobility challenges, cognitive changes, and vision issues. An estimated 1 million people live with MS in the United States. Early diagnosis and treatment are critical to minimize disability. Significant progress is being made to achieve a world free of MS.

About the National Multiple Sclerosis Society

The National MS Society, founded in 1946, is the global leader of a growing movement dedicated to creating a world free of MS. The Society funds cutting-edge research for a cure, drives change through advocacy and provides programs and services to help people affected by MS live their best lives. Connect to learn more and get involved:, Facebook, X, formerly known as Twitter, Instagram, YouTube or 1-800-344-4867.


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