, Volume 78, Issue 15, pp 1549–1566 | Cite as

Therapeutic Advances and Challenges in the Treatment of Progressive Multiple Sclerosis

  • Laura E. Baldassari
  • Robert J. FoxEmail author
Review Article


Despite the fact that majority of patients with multiple sclerosis (MS) have relapsing-remitting disease, many transition to secondary progressive disease (SPMS) over time. This transition is thought to be related to neurodegenerative processes increasingly predominating over inflammatory processes as the driving forces of disability. However, some patients initially present with primary progressive disease (PPMS) that is characterized by a gradual accumulation of neurological symptoms and subsequent disability accumulation. The treatment of both PPMS and SPMS, collectively referred to as progressive MS, has proven quite challenging due to the multifactorial and poorly understood pathophysiology of multiple sclerosis in general, specifically that of progressive disease. The purpose of this article is to discuss important clinical and pathophysiologic differences between relapsing and progressive forms of MS, review previous notable trials of drugs in progressive MS, examine current literature regarding recent and promising progressive MS treatments, and discuss future considerations for progressive MS therapeutics and management. Specifically, the current evidence regarding treatment of progressive MS with ocrelizumab, simvastatin, ibudilast, alpha-lipoic acid, high-dose biotin, siponimod, and cell-based therapies are discussed.


Compliance with Ethical Standards


No funding was received for the publication of this review.

Conflict of interest

Fox has received personal consultancy fees from Actelion, Biogen, EMD Serono, Genentech, Novartis, and Teva, and has served on advisory committees for Actelion, Biogen, and Novartis, and received clinical trial contract and research grant funding from Biogen and Novartis. Dr. Baldassari has received personal fees for serving on a scientific advisory board for Teva, and receives funding via a Sylvia Lawry Physician Fellowship Grant through the National Multiple Sclerosis Society (#FP-1606-24540).


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Mellen Center for Multiple Sclerosis Treatment and ResearchNeurological Institute, Cleveland ClinicClevelandUSA

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