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01-10-2017 | Review

Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis

Authors: Burhan Z. Chaudhry, Jeffrey A. Cohen, Devon S. Conway

Published in: Neurotherapeutics | Issue 4/2017

Abstract

Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor’s function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability. Fingolimod can cause undesirable effects as a result of its interaction with other S1PR subtypes, which are expressed in diverse tissues, including cardiac myocytes. As such, agents that more selectively target subtype 1 of the S1PR are of interest and are at various stages of development. These include ponesimod (ACT128800), siponimod (BAF312), ozanimod (RPC1063), ceralifimod (ONO-4641), GSK2018682, and MT-1303. Data from phase II trials and early results from phase III studies have been promising and will be presented in this review. Of special interest are results from the EXPAND study of siponimod, which suggest a potential role for S1PR modulators in secondary progressive MS.

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Title: Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis
Authors: Burhan Z. Chaudhry
Jeffrey A. Cohen
Devon S. Conway
Publication date: 01-10-2017
Publisher: Springer US
Published in: Neurotherapeutics / Issue 4/2017
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI: https://doi.org/10.1007/s13311-017-0565-4

At a glance: The STEP trials

Springer Medicine

Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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