FTY720 (Fingolimod) for Relapsing Multiple Sclerosis

Alejandro Horga; Xavier Montalban

Disclosures

Expert Rev Neurother. 2008;8(5):699-714. 

In This Article

Abstract and Introduction

FTY720 (fingolimod) is a structural analogue of sphingosine, an endogenous lysophospholipid, which targets sphingosine-1-phosphate receptors after biotransformation to FTY720-phosphate. The immunomodulatory properties of this agent are mainly related to its ability to entrap lymphocytes in secondary lymphoid organs, reducing their availability for cell-mediated immune responses. Emerging evidence suggests that FTY720 also exerts direct actions on glial and precursor cells of the CNS which may be relevant for the process of tissue repair after injury. The therapeutic effects of the drug observed in animal models of human multiple sclerosis have provided the experimental basis for its clinical application. A recent Phase II study has demonstrated that oral FTY720 is effective in reducing disease activity in relapsing multiple sclerosis with a favorable adverse-effect profile. These results are awaiting confirmation in the three ongoing Phase III clinical trials evaluating FTY720 for relapsing–remitting multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated disease of the CNS with a high potential for chronic disability, and considerable social and economic impact.[1] Disease onset usually occurs in the third to fourth decades of life. Although the clinical course of MS is heterogeneous, it may be considered as the combination of two phenomena: acute relapses, with partial or complete remission, and sustained progression of disability. For approximately 85% of patients, intermittent relapses are the sole clinical manifestation of MS during the first few years of the disease (relapsing–remitting MS). In a high proportion of these patients, which increases with disease duration, the clinical course of MS converts to a progressive phase with or without superimposed relapses (secondary-progressive MS). Two mechanisms underlie the impairment of CNS structure and function in MS patients: the formation of focal inflammatory demyelinating lesions, which dominates the pathological scenario in the relapsing phase, and a chronic widespread neurodegenerative process, which correlates with the progressive accumulation of disability. Autoreactive T cells are believed to drive the formation of MS lesions in the CNS. After T cells become activated in the periphery, they cross the BBB and trigger a cascade of events that finally result in myelin, oligodendrocyte and axonal injury.[2]

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