Louvet C et al. (2008) Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci USA 105: 18895–18900

The development of small-molecule tyrosine-kinase inhibitors, such as imatinib, has transformed cancer chemotherapy. Louvet and colleagues questioned whether these agents might also be effective in the treatment of autoimmune disorders, such as type 1 diabetes mellitus.

The authors treated nonobese, diabetic (NOD) mice with 1.5 mg imatinib or peanut oil once daily. Treatment with imatinib completely inhibited the development of diabetes mellitus in prediabetic NOD mice. By contrast, around 40% of prediabetic control mice developed diabetes mellitus. After cessation of treatment, diabetes mellitus developed in 20% of the imatinib-treated animals and in 71% of the control animals by 30 weeks of age. Treatment with imatinib was also found to reverse disease in NOD mice with new-onset diabetes mellitus. Furthermore, long-lasting remission occurred after a relatively short treatment period (10 weeks).

The precise mechanisms of the effect of imatinib on diabetes mellitus remain to be uncovered. Imatinib did not alter insulinitis, T-cell number or antigen-specific T-cell proliferation in NOD mice. One possibility that warrants further investigation, however, is specific inhibition of the platelet-derived growth-factor receptor.

Studies of imatinib in humans for the treatment of rheumatoid arthritis and Crohn disease are currently in progress. In light of their findings in the NOD mouse, Louvet et al. suggest that imatinib might also be considered as a potential therapy for patients with type 1 diabetes mellitus.