Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis
Abstract
The oral sphingosine 1-phosphate (S1P) receptor (S1PR) modulator fingolimod has been shown to be effective in the treatment of patients with relapsing multiple sclerosis (MS). The drug binds with high affinity to 4 of the 5 G-protein–coupled S1P receptors (S1P1–5). After binding, the receptors are internalized, degraded, and thus functionally antagonized by fingolimod. Under physiologic conditions, S1P1 mediates the egress of lymphocytes from secondary lymphoid organs to the peripheral circulation. Functional antagonism of S1P1 by fingolimod results in a reduction in peripheral lymphocyte counts by inhibiting egress of lymphocytes, including potentially encephalitogenic T cells and their naïve progenitors that would otherwise be present within the circulation. Despite the fingolimod-mediated reduction of lymphocyte counts, fingolimod-treated patients with MS have been shown to have few infections and related complications and were able to mount antigen-specific immune responses in vaccination studies.
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Information & Authors
Information
Published In
Neurology®
Volume 76 • Number 8_supplement_3 • February 22, 2011
Pages: S20-S27
Copyright
Copyright © 2011 by AAN Enterprises, Inc.
Publication History
Published online: February 21, 2011
Published in print: February 22, 2011
Authors
Disclosure
Dr. Mehling reports receiving research support from the Swiss Multiple Sclerosis Society. Dr. Johnson reports no disclosures. Dr. Antel reports having received consulting fees for serving on advisory boards, including data safety monitoring committees, from Teva, Merck-Serono, Novartis, Actelion, Biogen-Idec, GSK and Sanofi-Aventis, and has received grant support for studies related to the effects of fingolimod on the CNS from Novartis. Dr. Kappos reports receiving research support from Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill Therapeutics, Biogen-Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck-Serono, MediciNova, Novartis, Novo Nordisk, Peptimmune, Sanofi-Aventis, Santhera, Roche, Teva, UCB, and Wyeth. Dr. Bar-Or reports receiving personal compensation for consulting, serving on scientific advisory boards, and/or speaking activities from Bayer, Bayhill Therapeutics, Berlex, Biogen-Idec, BioMS, Diogenix, Eli-Lilly, Genentech, GSK, Guthy-Jackson/GGF, Merck-Serono, Novartis, Ono, Roche, Teva Neuroscience, and Wyeth. He has received research funding from Bayhill Therapeutics, Biogen-Idec, Genentech, and Teva Neuroscience, and has received research support from the Multiple Sclerosis Society of Canada and the Canadian Institutes of Health Research. Dr. Bar-Or has served on scientific advisory boards for the following within the past 2 years: BioMS, Diogenix, Ono Pharmacia, and Roche; and serves on the following editorial boards: Clinical & Experimental Neuroimmunology and Neurology®.
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