Idebenone: an emerging therapy for Friedreich ataxia.

This paper reviews the history and pre-clinical development of idebenone and summarises the results of clinical studies, published from 1999 to 2008, on the use of idebenone in the treatment of patients with Friedreich ataxia (FRDA). As a benzoquinone that can undergo reversible redox reactions, idebenone influences the electron balance in mitochondria. In vitro studies have shown that it acts both as an anti-oxidant, preventing damage to the mitochondrial membrane, and, more importantly, as an electron carrier, supporting mitochondrial function and adenosine triphosphate (ATP) production. In clinical studies, idebenone has been well tolerated by patients with various pathological conditions. The most common adverse events have been gastrointestinal effects of mild to moderate severity. No neurotoxic or adverse cardiac reactions have been reported in pre-clinical or clinical studies. The good safety profile of idebenone is supported by large clinical trials in Alzheimer's disease and by post-marketing surveillance. Phase 1 studies demonstrated the safety and tolerability of idebenone at relatively high doses (up to 60 mg/kg/day). Results from 11 clinical studies (randomised, controlled, and open-label trials), involving a total of about 200 patients, provide evidence of improvement in both cardiac hypertrophy and neurological symptoms among patients with FRDA treated with idebenone.