Brain sphingosine-1-phosphate receptors: Implication for FTY720 in the treatment of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune, neurological disability with unknown etiology. The current therapies available for MS work by all immunomodulatory action, preventing T-cell- and macrophage-mediated destruction of brain-resident oligodendrocytes and axonal loss. Recently, FTY720 (fingolimod) was shown to significantly reduce relapse rates in MS patients and is currently in Phase III clinical trials. This drug attenuates trafficking of harmful T cells entering the brain by regulating sphingosine-1-phosphate (SIP) receptors. Here, we outline the direct roles that S I P receptors play in the central nervous system (CNS) and discuss additional modalities by which FTY720 may provide direct neuroprotection in MS. (c) 2007 Elsevier Inc. All rights reserved.