Bioavailable central nervous system disease-modifying therapies for multiple sclerosis

Hans-Peter Hartung; Bruce A C Cree; Michael Barnett; Sven G Meuth; Amit Bar-Or; Lawrence Steinman

doi:10.3389/fimmu.2023.1290666

Bioavailable central nervous system disease-modifying therapies for multiple sclerosis

Front Immunol. 2023 Nov 29:14:1290666. doi: 10.3389/fimmu.2023.1290666. eCollection 2023.

Authors

Hans-Peter Hartung^{1 2 3 4}, Bruce A C Cree⁵, Michael Barnett², Sven G Meuth¹, Amit Bar-Or⁶, Lawrence Steinman⁷

Affiliations

¹ Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
² Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
³ Department of Neurology, Medical University of Vienna, Vienna, Austria.
⁴ Department of Neurology, Palacký University Olomouc, Olomouc, Czechia.
⁵ Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, United States.
⁶ Center for Neuroinflammation and Experimental Therapeutics, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
⁷ Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA, United States.

Abstract

Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease where cells in the central nervous system play a critical role. To our knowledge, alemtuzumab, fumarates (dimethyl, diroximel, and monomethyl), glatiramer acetates, interferons, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and teriflunomide are either limited to the periphery or insufficiently studied to confirm direct central nervous system effects in participants with multiple sclerosis. In contrast, cladribine and sphingosine 1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are central nervous system-penetrant and could have beneficial direct central nervous system properties.

Keywords: central nervous system; cladribine; fingolimod hydrochloride; multiple sclerosis; ozanimod; ponesimod; siponimod; sphingosine 1 phosphate receptor modulators.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Central Nervous System Diseases*
Cladribine
Humans
Immunosuppressive Agents
Multiple Sclerosis* / drug therapy
Multiple Sclerosis, Relapsing-Remitting*

Substances

Immunosuppressive Agents
Cladribine

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors declare that this review project received funding from Bristol Myers Squibb (Princeton, NJ) for writing and editorial assistance. The funder was not involved in the design, literature review, interpretation, the writing of this article, or the decision to submit it for publication.