Advances in Gene and Cellular Therapy in Friedreich Ataxia.

Abstract

Friedreich ataxia is a rare, autosomal recessive neurogenerative disorder caused by mutations to the frataxin (FXN) gene resulting in loss of functional FXN protein. Applications of cutting-edge genetic and cellular therapies expand therapeutic options for patients with rare, genetic diseases including Friedreich ataxia. Multiple investigational techniques and strategies seek to permanently alter the disease course in patients with Friedreich ataxia, although no product has established definitive benefit. This review catalogs both the history and ongoing efforts of genetic and cellular therapies applied to Friedreich ataxia and its disease models, including therapeutic efficacy and adverse effects. We list the key limitations and cautions of such therapies, chiefly those of potential FXN overexpression toxicity, critical therapeutic windows, and adverse effects of these therapies applicable to any disease target. As gene and cellular therapy continue to diversify in design and strategy, Friedreich ataxia patients will likely have multiple therapeutic options in the future from both investigational therapies described here and future ones yet to be optimized.