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Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis

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Abstract

Sphingosine 1-phosphate (S1P) receptor modulators possess a unique mechanism of action as disease-modifying therapy for multiple sclerosis (MS). Subtype 1 S1P receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes. The S1P receptor modulators indirectly antagonize the receptor’s function and sequester lymphocytes in lymph nodes. Fingolimod was the first S1P agent approved in the USA in 2010 for relapsing MS after two phase III trials (FREEDOMS and TRANSFORMS) demonstrated potent efficacy, and good safety and tolerability. Post-marketing experience, as well as a third phase III trial (FREEDOMS II), also showed favorable results. More selective S1P receptor agents—ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303—are still in relatively early stages of development, but phase I and II trials showed promising efficacy and safety. However, these observations have yet to be reproduced in phase III clinical trials.

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Authors and Affiliations

  1. Mellen Center for MS Treatment and Research, Cleveland Clinic Foundation, 9500 Euclid Avenue/U10, Cleveland, OH, 44195, USA

    Adnan M. Subei & Jeffrey A. Cohen

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  1. Adnan M. Subei
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  2. Jeffrey A. Cohen
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Correspondence to Jeffrey A. Cohen.

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Conflicts of interest

AM Subei has nothing to disclose. JA Cohen is an editor of Multiple Sclerosis Journal—Experimental, Translational and Clinical and reports personal fees from EMD Serono, Genentech, Genzyme, Novartis, Receptos, Teva, and Vaccinex for consulting.

Funding

AM Subei is supported by Clinician Care Fellowship Award CF 00104N-1 from the National Multiple Sclerosis Society, which funded the time allocated to developing the manuscript. Otherwise no direct funding was received.

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Subei, A.M., Cohen, J.A. Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis. CNS Drugs 29, 565–575 (2015). https://doi.org/10.1007/s40263-015-0261-z

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