Progress and prospects for treating ataxia telangiectasia

Introduction: Ataxia Telangiectasia (AT) is an autosomal recessive disorder due to mutations in the ATM gene (11q22.3), which encodes a kinase, which initiates and propagates the cellular response to severe DNA lesions. Cerebellar ataxia, ocular and skin telangiectasia, immunodeficiency, cardiovascular, liver and endocrine defects, and predisposition to malignancies characterize the classical form of AT. Milder forms and AT-like disorders (ATLD) have later onset or slower progression. ATM carriers are at increased risk for cancer and other diseases. Areas covered: We reviewed the most updated treatments of AT from 2014. A proactive monitoring and early treatment of respiratory manifestations, growth, nutrition, cardiovascular defects, liver and metabolism and oxidative stress, are the most challenging issues. Steroids improved neurodegeneration with some limitations. The alternative roles of the ATM kinase in cell homeostasis via signalling pathways [e.g. mTORC1, Akt, ROS, PDGFRB] control, nuclear (in developing cells) vs. cytoplasmic functions (in post-mitotic cells) are reviewed. Expert opinion: AT demands a multidisciplinary specialized model of care aided by pharmacological and non-pharmacological interventions. Dexamethasone (clinically) and ibuprofen (experimentally) received positive assessment for neurological and inflammatory disturbances. Gene and stem cell therapies are in progress.