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Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications

  • Demyelinating Disorders (J. Bernard and M. Cameron, Section Editors)
  • Published:
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Abstract

Purpose of Review

Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). Inflammatory attacks in MS lead to both demyelination and axonal damage. However, due to incomplete remyelination most MS lesions remain chronically demyelinated. In parallel, there is axonal degeneration in the CNS of MS patients, contributing to progressive disability. There are currently no approved therapies that adequately restore myelin or protect axons from degeneration. In this review, we will discuss the pathophysiology of axonal loss and chronic demyelination in MS and how understanding this pathophysiology is leading to the development of new MS therapeutics.

Recent Findings

Ongoing research into the function of oligodendrocytes and myelin has revealed the importance of their relationship with neuronal health. Demyelination in MS leads to a number of pathophysiologic changes contributing to axonal generation. Among these are mitochondrial dysfunction, persistent neuroinflammation, and the effects of reactive oxygen and nitrogen species. With this information, we review currently approved and investigational therapies designed to restore lost or damaged myelin and protect against neuronal degeneration.

Summary

The development of therapies to restore lost myelin and protect neurons is a promising avenue of investigation for the benefit of patients with MS.

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Acknowledgements

The authors would like to thank Ben Emery for reviewing the manuscript and providing insightful feedback contributing to the final version. The figure was created with BioRender.com.

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  1. Department of Neurology, Oregon Health and Science University, 3181S W Sam Jackson Rd L226, Portland, OR, 97239, USA

    Tyrell J Simkins, Greg J Duncan & Dennis Bourdette

  2. Jungers Center for Neurosciences Research, Oregon Health and Science University, Portland, OR, USA

    Tyrell J Simkins, Greg J Duncan & Dennis Bourdette

  3. Department of Neurology, Portland VA Medical Center, Portland, OR, USA

    Tyrell J Simkins

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T.S. and D.B. devised the manuscript. T. S, G.D., and D.B wrote/revised the manuscript.

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T.S. reports no conflict of interest. G.D. reports no conflict of interest. D.B. is a co-founder of Autobahn Therapeutics.

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Simkins, T.J., Duncan, G.J. & Bourdette, D. Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications. Curr Neurol Neurosci Rep 21, 26 (2021). https://doi.org/10.1007/s11910-021-01110-5

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