Prospects of gene and cell therapy for managing cardiac complications in Friedreich ataxia

Abstract

Introduction: Friedreich ataxia (FRDA) is a progressive neurodegenerative disease affecting ∼ 1/50,000 people. The disease is caused by guanine–adenine–adenine repeat expansions in the frataxin gene, which results in frataxin deficiency. Cardiac complications occur in a majority of patients and are the leading cause of death in FRDA. Presently, there are no therapeutic agents to slow the disease progression. Recently, gene and cell therapies have been proposed as future treatments for addressing the debilitating cardiac features of the disease.Areas covered: This review describes potential gene and cell therapy approaches to treating cardiac complications in FRDA. Cell therapies include induced pluripotent stem cells and bone marrow-derived mesenchymal stem cells. Gene therapy options consist of lentiviral, herpes simplex virus and adeno-associated virus (AAV) vectors for gene transfer, with AAV-frataxin vectors reaching late preclinical stages of testing.Expert opinion: Gene and cell therapies are progressing toward clinical trials, with encouraging outcomes noted for mesenchymal stem cell therapy and AAV gene therapy in mouse models. Current limitations are largely technical; issues of immunogenicity and duration of benefits suggest that any treatment consisting of gene or cell therapy will require combinations of other drugs. AAV gene therapy offers the prospect of improving cardiac outcomes for the patient population of FRDA.