Pioglitazone as a Possible Treatment for Ataxia-Telangiectasia.

Abstract

Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder characterized by immunodeficiency, progressive cerebellar ataxia, and an increased malignancy risk. Cells derived from individuals with AT show multiple defects, including high oxidant and ionizing radiation sensitivities, poor DNA repair, low iron-sulfur cluster levels, and low reduced glutathione. The clinical course of AT is progressive and unrelenting, with most individuals having a survival time of approximately twenty-five years. Presently, AT has no effective treatments, and most patients receive supportive care only. Recently, pioglitazone, a thiazolidinedione class used to treat type 2 diabetes, has been demonstrated to exert beneficial effects on AT cells and on diabetic individuals with AT. Here, I will discuss the possible molecular mechanisms of pioglitazone's favorable effects on the AT phenotype and why it may have utility in treating some aspects of AT.