Treatment of Friedreich's ataxia

Introduction: Advances in understanding the pathogenesis of Friedreich's ataxia (FRDA) allowed the development of new therapeutic strategies. Approaches to increase frataxin levels aim to alleviate the epigenetic transcriptional silencing of the frataxin gene by expanded GAA repeats, or to induce frataxin expression regardless of the expansion mutation. Other therapeutic targets are mitochondrial dysfunction, altered iron metabolism and oxidative damage. Areas covered: The pathogenesis of FRDA is summarized in order to highlight potential therapeutic targets. The available animal and cellular models for preclinical testing, clinical assessment tools and biomarkers are reviewed. The rationale behind each compound currently in the development pipeline is provided and the results of preclinical and clinical studies are reviewed. Information was obtained by searching PubMed, from the ClinicalTrials.gov website, from communications at meetings and personal communications. Expert opinion: So far, randomized controlled trials have not provided robust evidence of efficacy for any of the tested molecules. However, some compounds currently in the pipeline appear very promising. Important objectives include the development of better cellular and animal models for preclinical testing, and the improvement of trial design. Ongoing large natural history studies, which evaluate clinical assessment tools and biomarkers, are providing essential guidance.