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Re-defining progression in multiple sclerosis
Jeffrey Lambe1, Daniel Ontaneda
1Mellen Center for Multiple Sclerosis Treatment and Research, Neurology Department, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Purpose Of Review:
The purpose of this article is to provide an overview of progression in multiple sclerosis (MS), including definitions, pathological mechanisms, and evidence that progressive biology begins early in the disease course.
Recent Findings:
Definitions of MS clinical course have been refined to acknowledge the presence of both relapse and progression biology throughout the disease. Progression independent of relapse activity represents a significant proportion of disability worsening in relapsing-remitting MS (RRMS) disease. Progression in MS appears to be caused by the complex interplay of multiple processes, including nonresolving inflammation, microglial activation, oxidative stress, mitochondrial dysfunction, energetic failure, and neuro-axonal degeneration. These processes appear to begin in the earliest disease stages and their contribution to clinical phenotypes is dynamic over time. Promising results from clinical trials of tolebrutinib, in particular, underline the utility of targeting both innate and adaptive immune mechanisms to reduce disability accumulation.
Summary:
Pathological processes that underpin MS progression are detectable early in RRMS, evolve throughout the disease course and correlate with disability accumulation. Progression in MS should not be defined dichotomously - the focus instead should be on recognizing progressive components based on clinical measures and biomarkers early in the disease to better individualize treatment strategies.
Insights
Multiple sclerosis (MS) progression begins early, driven by inflammation and neurodegeneration. Recognizing these early progressive components is key for personalized treatment strategies in relapsing-remitting MS (RRMS).
Area of Science:
- Neurology
- Immunology
- Pathology
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
- Clinical course definitions are evolving to include progression alongside relapses.
Purpose of the Study:
- To review the progression of multiple sclerosis (MS).
- To define pathological mechanisms driving MS progression.
- To present evidence of early progressive biology in MS.
Main Methods:
- Review of existing literature on MS progression.
- Analysis of pathological mechanisms.
- Examination of clinical trial data, including tolebrutinib.
Main Results:
- Progression independent of relapses contributes significantly to disability in relapsing-remitting MS (RRMS).
- MS progression involves inflammation, microglial activation, oxidative stress, and neurodegeneration.
- These pathological processes are evident early in the disease and evolve over time.
Conclusions:
- MS progression is a continuous process detectable early in RRMS.
- Pathological drivers of progression correlate with disability.
- Individualized treatment strategies require early identification of progressive components using clinical measures and biomarkers.
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