Takashi Maki1, Rita Gottschalk, Anthony P Monaco. 1. Transplant Center, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. tmaki@caregroup.harvard.edu.
Abstract
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.
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.
Authors: Alaa S Awad; Michael D Rouse; Konstantine Khutsishvili; Liping Huang; W Kline Bolton; Kevin R Lynch; Mark D Okusa Journal: Kidney Int Date: 2011-02-02 Impact factor: 10.612
Authors: S M Dudek; S M Camp; E T Chiang; P A Singleton; P V Usatyuk; Y Zhao; V Natarajan; J G N Garcia Journal: Cell Signal Date: 2007-04-06 Impact factor: 4.315