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Updated: Jul 8, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Toward identifying key mechanisms of progression in multiple sclerosis
Leila Husseini1, Anastasia Geladaris2, Martin S Weber3
1Department of Neurology, University Medical Center, Göttingen, Germany.
Abstract:
A major therapeutic goal in the treatment of multiple sclerosis (MS) is to prevent the accumulation of disability over an often decades-long disease course. Disability progression can result from acute relapses as well as from CNS intrinsic parenchymal disintegration without de novo CNS lesion formation. Research focus has shifted to progression not associated with acute inflammation, as it is not sufficiently controlled by currently available treatments. This review outlines how recent advances in the understanding of the pathogenesis of progressive MS have been facilitated by the development of more precise, less static pathogenetic concepts of progressive MS, as well as by new techniques for the analysis of region-specific proteomic and transcriptomic signatures in the human CNS. We highlight key drivers of MS disease progression and potential targets in its treatment.
Insights
Preventing disability in multiple sclerosis (MS) requires understanding progressive disease beyond inflammation. New insights into CNS pathogenesis and molecular signatures offer novel therapeutic targets for MS progression.
Area of Science:
- Neuroimmunology
- Neurobiology
- Molecular Medicine
Background:
- Multiple sclerosis (MS) treatment aims to prevent long-term disability accumulation.
- Disability progression in MS occurs through acute relapses and chronic neurodegeneration.
- Current treatments inadequately address progressive MS not linked to acute inflammation.
Purpose of the Study:
- To review advances in understanding the pathogenesis of progressive MS.
- To highlight new techniques for analyzing CNS molecular signatures.
- To identify key drivers of MS progression and potential therapeutic targets.
Main Methods:
- Review of recent scientific literature on MS pathogenesis.
- Analysis of new techniques for proteomic and transcriptomic profiling of the human CNS.
- Synthesis of current understanding of progressive MS mechanisms.
Main Results:
- Development of more precise pathogenetic concepts for progressive MS.
- Advancements in analyzing region-specific proteomic and transcriptomic signatures.
- Identification of key molecular drivers contributing to MS disease progression.
Conclusions:
- Understanding progressive MS requires moving beyond inflammation-centric models.
- Molecular signatures in the CNS offer insights into disease mechanisms.
- Targeting identified drivers presents new therapeutic opportunities for progressive MS.
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