Prevention of autoimmune diabetes by FTY720 in nonobese diabetic mice

BACKGROUND: FTY720 prevents allograft rejection with remarkable potency without inducing generalized immunosuppression. We determined the effect of FTY720 on development of autoimmune diabetes in nonobese diabetic (NOD) mice. METHODS: NOD mice were given FTY720 (0.5 mg/kg, orally) five times per week starting from 4 weeks of age. RESULTS: Daily FTY720 prevented development of diabetes in 15 of 16 treated mice, whereas 70% of untreated NOD mice became diabetic by 35 weeks of age. Withdrawal of FTY720 at 35 weeks of age led to development of diabetes within 2 weeks in five mice, whereas the remaining mice maintained diabetes-free conditions for up to 44 weeks of age. No side effect of the drug was seen throughout the treatment period. FTY720 also prevented cyclophosphamide-induced diabetes in NOD mice. CONCLUSIONS: FTY720 is a safe and benign therapeutic agent that may be used chronically in prediabetic individuals.