一种用于治疗白血病的药物也能逆转糖尿病模型小鼠的糖尿病。Cédric Louvet及其同事的一项新研究表明，伊马替尼（格列卫®）和另一种酪氨酸激酶抑制剂药物，可以通过抑制小鼠的免疫系统从而防止或逆转小鼠的I型糖尿病。伊马替尼是被用来抑制慢性骨髓性白血病中出现的一种特定的酪氨酸激酶，但是这种药物也会抑制其它酪氨酸激酶，其中好几种存在于免疫系统中。

I型糖尿病是一种自体免疫疾病，是由炎症摧毁了胰腺细胞造成的。为了测试伊马替尼是否能改善这种炎症从而阻止糖尿病的发生，这组科学家在糖尿病小鼠模型身上测试了该药。在这个过程中，他们发现用伊马替尼或一种类似的抑制剂药物对小鼠的自体免疫（I型）糖尿病发作前进行7周的治疗，可以在治疗停止之后很久防止该病的发展。当发病之后对小鼠进行8-10周的治疗后，该药还让80%的患病小鼠的症状缓和。这组作者说，这种有效性表明这种对癌症治疗有重要作用的药物也可以用于治疗I型糖尿病，或许还能治疗其他自体免疫疾病。相关论文发表在美国《国家科学院院刊》（PNAS）上。

推荐原始出处：

PNAS，doi: 10.1073/pnas.0810246105，Cédric Louvet，Jeffrey A. Bluestone

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice

Cédric Louveta, Gregory L. Szota, Jiena Langa, Michael R. Leea, Nicolas Martiniera, Gideon Bollagb, Shirley Zhua, Arthur Weissc,1, and Jeffrey A. Bluestonea,1

aDiabetes Center and the Department of Medicine, University of California, San Francisco, CA 94143;
bPlexxikon, Berkeley, CA 94710; and
cDepartment of Medicine and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94143

Abstract

The recent development of small-molecule tyrosine kinase (TK) inhibitors offers increasing opportunities for the treatment of autoimmune diseases. In this study, we investigated the potential of this new class of drugs to treat and cure type 1 diabetes (T1D) in the NOD mouse. Treatment of prediabetic and new onset diabetic mice with imatinib (Gleevec) prevented and reversed T1D. Similar results were observed with sunitinib (Sutent), an additional approved multikinase inhibitor, suggesting that the primary target of imatinib, c-Abl, was not essential in blocking disease in this model. Additional studies with another TK inhibitor, PLX647 (targeting c-Kit and c-Fms) or an anti-c-Kit mAb showed only marginal efficacy whereas a soluble form of platelet-derived growth factor receptor (PDGFR), PDGFRβIg, rapidly reversed diabetes. These findings strongly suggest that inhibition of PDGFR is critical to reverse diabetes and highlight a crucial role of inflammation in the development of T1D. These conclusions were supported by the finding that the adaptive immune system was not significantly affected by imatinib treatment. Finally, and most significantly, imatinib treatment led to durable remission after discontinuation of therapy at 10 weeks in a majority of mice. Thus, long-term efficacy and tolerance is likely to depend on inhibiting a combination of tyrosine kinases supporting the use of selective kinase inhibitors as a new, potentially very attractive approach for the treatment of T1D.