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  • Review Article
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Multiple sclerosis—a quiet revolution

Nature Reviews Neurology volume 11, pages 134–142 (2015)Cite this article

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A Corrigendum to this article was published on 24 March 2015

This article has been updated

Key Points

  • MS has been a treatable disease for approximately 20 years, and incremental improvements in treatment options have culminated in remarkable progress for the amelioration of inflammatory aspects of MS

  • Traditionally, three patterns of disease evolution (relapsing–remitting, secondary progressive and primary progressive) were recognized, but present evidence suggests that these differing clinical phenotypes share common pathophysiology

  • A major unmet medical need in MS therapeutics is to define biomarkers to aid selection from the several treatment options so that individual patients can receive optimal personalized therapy

  • The requirement that patients fail IFN-β and glatiramer acetate therapy before being offered alternatives risks irreversible neural tissue injury during the process of initiating appropriate medication

  • Early, general statements that implicated a genetic component in multiple sclerosis (MS) susceptibility have been replaced by the identification of more than 100 genetic variants associated with disease susceptibility, ∼90% of which are noncoding

  • Over half of genetic variants associated with MS risk are also found in other autoimmune diseases, and are primarily associated with genes that regulate immune function

Abstract

Multiple sclerosis (MS) has been thought to be a complex and indecipherable disease, and poorly understood with regards to aetiology. Here, we suggest an emphatically positive view of progress over several decades in the understanding and treatment of MS, particularly focusing on advances made within the past 20 years. As with virtually all complex disorders, MS is caused by the interaction of genetic and environmental factors. In recent years, formidable biochemical, bioinformatic, epidemiological and neuroimaging tools have been brought to bear on research into the causes of MS. While susceptibility to the disease is now relatively well accounted for, disease course is not and remains a salient challenge. In the therapeutic realm, numerous agents have become available, reflecting the fact that the disease can be attacked successfully at many levels and using varied strategies. Tailoring therapies to individuals, risk mitigation and selection of first-line as compared with second-line medications remain to be completed. In our view, the MS landscape has been comprehensively and irreversibly transformed by this progress. Here we focus on MS therapeutics—the most meaningful outcome of research efforts.

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Figure 1: Timeline for the development of disease-modifying drugs for MS.

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Change history

  • 24 March 2015

    In the version of this article initially published online, the Competing interests section was incomplete. The error has been corrected for the PDF and HTML versions of the article.

  • 19 February 2015

    In the version of this article initially published online, the Acknowledgements section was incomplete. The error has been corrected for the print, PDF and HTML versions of the article.

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Acknowledgements

D.A.H.'s work was supported by a National MS Society Collaborative Research Centre Award CA1061-A-18, NIH grants P01 AI045757, U19 AI046130, U19 AI070352, and P01 AI039671, the Penates Foundation and the Nancy Taylor Foundation for Chronic Diseases, Inc. C.F.L. is supported by a grant from the NIH, R01-NS049577-01-A2.

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Authors and Affiliations

  1. Biogen Idec, 14 Cambridge Centre, Cambridge, 02142, MA, USA

    Richard M. Ransohoff

  2. Departments of Neurology and Immunobiology, Yale School of Medicine, 15 York Street, New Haven, 06520, CT, USA

    David A. Hafler

  3. Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, 55905, MN, USA

    Claudia F. Lucchinetti

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The authors contributed equally to the researching of data for and writing of the article, and each made substantial contributions to the discussion of content and the revision/editing of the manuscript before submission.

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Correspondence to David A. Hafler.

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Competing interests

R.M.R. is a full-time employee of Biogen. However, this article was written and submitted while he worked at the Cleveland Clinic. D.A.H. has consulted for Allergan Pharmaceuticals, Bristol-Myers Squibb, EMD Serono, Genzyme Sanofi-Aventis, MedImmune, Mylan Pharmaceuticals, Novartis Pharmaceuticals, Questcor and Teva Neuroscience. C.F.L. declares no competing interests.

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Ransohoff, R., Hafler, D. & Lucchinetti, C. Multiple sclerosis—a quiet revolution. Nat Rev Neurol 11, 134–142 (2015). https://doi.org/10.1038/nrneurol.2015.14

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