T. Böhler, J. Waiser, M. Schütz, K. Budde
FTY720: Development of a Novel and Unique, Immunmodulating Drug that has the Potential to Revolutionize Transplantation Medicine

FTY720 (FTY) is a new immunmodulating agent to prevent allograft rejection. In animal models FTY exerts synergism with cyclosporine. Recently, a multicenter phase II trial in renal allograft recipients was successfully performed. FTY, in combination with cyclosporine and steorids is safe and efficient to prevent graft rejection.
FTY is slowly absorbed and exerts a half-life of 144 hours. The maximum blood concentration is reached within 24 hours which is consistant with a gastro-intestinal absorption. FTY is metabolized by cytochrome CyP4F and by ß-oxidation.
Preclinical studies revealed that FTY uses EDG6 as an receptor. EDG6 is a G-protein coupled receptor for the natural ligand sphingosine-1-phosphate. EDG6 is mainly expressed on the surface of lymphocytes and induces a reversible lymphopenia by an apoptosis independent mechanism. This lymphopenia is induced by an modified lymphocyte trafficking which results in an altered composition lymphocyte subsets in the peripheral blood compartment. It is thought that the altered lymphocyte re-circulation pattern prevents the infiltration of lymphocytes into the graft.
In this paper I will review the recent preclinical, pharmacological and clinical research on FTY and will discuss the novel strategy of immunosuppression by FTY.

Key words: FTY720, EDG-6, transplantation, immunosuppression, lymphocyte homing, CCR5, CD62-L

Dr. Torsten Böhler
Medizinische Klinik mit Schwerpunkt Nephrologie
Humboldt-Universität Berlin
Charité, Campus Mitte
Schumannstr. 20/21
D-10117 Berlin
E-mail: torsten.boehler@charite.de