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.

Brain and Mind Centre University of Sydney Sydney NSW Australia

Center for Neuroinflammation and Experimental Therapeutics Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA United States

Department of Neurology and Neurological Sciences Beckman Center for Molecular Medicine Stanford University Medical Center Stanford CA United States

Department of Neurology Medical Faculty Heinrich Heine University Düsseldorf Germany

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Palacký University Olomouc Olomouc Czechia

Weill Institute for Neurosciences Department of Neurology University of California San Francisco San Francisco CA United States

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