Fingolimod - development of signal transduction inhibitors for the therapy of multiple sclerosis

Signal transduction processes (communication from extra- to intracellular compartments) are involved in a plethora of physiologic and pathologic processes. Molecular analyses identified a variety of molecules that have currently led to novel therapy strategies in solid and hematologic malignancies. This increased understanding of signal transduction cascades has now been applied successfully with Fingolimod (FTY720) in two phase III trials of multiple sclerosis. Fingolimod is a sphingosine-l-phosphate receptor-modulator and a functional antagonist of sphingosine-1-phosphate (SIP), which binds to different G-protein coupled transmembrane receptors and modulates immunologic, vascular and cell biologic processes. In the CNS, S1P also regulates the egress of lymphocytes from blood vessels and promotes proliferation of astrocytes, which is associated with the pathogenesis of neurodegenerative diseases with astrogliosis. In this article, the basic underlying molecular and biochemical processes of Fingolimod will be reviewed and the therapeutic effect in multiple sclerosis will be discussed.