The multi-tyrosine kinase inhibitor, imatinib, primarily used to treat chronic myeloid leukaemia (CML), has been shown to exert immunomodulatory and anti-inflammatory effects, achieving promising results both in mouse models and several Phase I trials of autoimmune diseases such as rheumatoid arthritis and psoriasis. In addition, improvements in type 2 diabetes have been noted in patients with CML on imatinib therapy. Moreover, imatinib was recently shown to prevent β-cell apoptosis under conditions of β-cell stress. Together, these observations led Louvet and colleagues to develop the hypothesis that imatinib may also be beneficial in the treatment of T1D.
Using the non-obese diabetic (NOD) mouse model, the authors first assessed the effects of imatinib in both pre- and established diabetes. None of the 12-week-old prediabetic mice treated with a 7-week course of imatinib developed the disease, in contrast to 40% of controls. Furthermore, following treatment termination, just 20% of treated mice became progressively diabetic at 30 weeks of age, compared with 71% of controls. In fact, the majority of imatinib-treated mice remained non-diabetic for more than 50 weeks, suggesting that short-term imatinib therapy achieved lasting effects. Remarkably, initiation of imatinib at the time of disease onset proved similarly beneficial, with 80% of mice exhibiting remission within 2 weeks of treatment. Ten-week treatment predominantly resulted in long-term remission.
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