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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.
Footnotes
This Neurology® supplement is not peer-reviewed. Information contained in this Neurology® supplement represents the opinions of the authors. These opinions are not endorsed by nor do they reflect the views of the American Academy of Neurology, Editor-in-Chief, or Associate Editors of Neurology®.
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- EAE
- experimental autoimmune encephalomyelitis
- FDA
- Food and Drug Administration
- IFN
- interferon
- IgG
- immunoglobulin G
- IL
- interleukin
- KLH
- keyhole limpet hemocyanin
- LN
- lymph nodes
- MS
- multiple sclerosis
- NK cells
- natural killer cells
- PPV-23
- pneumococcal polysaccharide vaccine-23
- S1P
- sphingosine 1-phosphate
- S1P1–5
- S1P receptor subtypes 1–5
- S1PR
- sphingosine 1-phosphate receptor
- TCM
- central memory T cells
- TEM
- effector memory T cells
- TEMRA
- CD45RA-expressing TEM.
- Copyright © 2011 by AAN Enterprises, Inc.
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