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  • Title: Targeting JAK3 with JANEX-1 for prevention of autoimmune type 1 diabetes in NOD mice.
    Author: Cetkovic-Cvrlje M, Dragt AL, Vassilev A, Liu XP, Uckun FM.
    Journal: Clin Immunol; 2003 Mar; 106(3):213-25. PubMed ID: 12706408.
    Abstract:
    Here we show that Janus kinase (JAK) 3 is an important molecular target for treatment of autoimmune insulin-dependent (type 1) diabetes mellitus. The rationally designed JAK3 inhibitor JANEX-1 exhibited potent immunomodulatory activity and delayed the onset of diabetes in the NOD mouse model of autoimmune type 1 diabetes. Whereas 60% of vehicle-treated control NOD mice became diabetic by 25 weeks, the incidence of diabetes at 25 weeks was only 9% for NOD females treated with daily injections of JANEX-1 (100 mg/kg/day) from Week 10 through Week 25 (P = 0.007). Furthermore, JANEX-1 prevented the development of insulitis and diabetes in NOD-scid/scid females after adoptive transfer of splenocytes from diabetic NOD females. Chemical inhibitors such as JANEX-1 may provide the basis for effective treatment modalities against human type 1 diabetes. To our knowledge, this is the first report of the immunosuppressive activity of a JAK3 inhibitor in the context of an autoimmune disease.
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