Clinical experience with high-dose idebenone in Friedreich ataxia

• Published in: Journal of neurology Vol. 256; no. Suppl 1; pp. 42 - 45
• Main Authors: Schulz, Jörg B., Di Prospero, Nicholas A., Fischbeck, Kenneth
• Format: Journal Article
• Language: English
• Published: Darmstadt Steinkopff-Verlag 01.03.2009; Springer Nature B.V
• Subjects: Antioxidants - therapeutic use; Ataxia; Cardiomyopathies - drug therapy; Cardiomyopathies - etiology; Cardiomyopathy; Clinical Protocols; Clinical trials; Clinical Trials as Topic - methods; Dose-Response Relationship, Drug; Friedreich Ataxia - complications; Friedreich Ataxia - drug therapy; Heart; Humans; Medicine; Medicine & Public Health; Nervous System Diseases - drug therapy; Nervous System Diseases - etiology; Neurology; Neuroradiology; Neurosciences; Oxidative stress; Ubiquinone - analogs & derivatives; Ubiquinone - therapeutic use; Aachen Germany; United States > US; Germany; rare disorders; Friedreich ataxia; clinical trials; cardiomyopathy; ICARS; FARS; neurologic; oxidative stress; idebenone
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-009-1008-x

Several reports in the literature describe the effects of low-dose (5 mg/kg/day) idebenone in significantly reducing cardiac hypertrophy in patients with Friedreich ataxia. However, the effects of idebenone on neurological function have not been reliably determined in these studies; when neurological parameters were reported, results were often inconclusive, usually because of subject heterogeneity and lack of adequate statistical power. In two of these studies, some patients showed beneficial effects of idebenone on their cardiomyopathy only when the dose was increased, prompting the systematic investigation of higher doses of idebenone. Following a phase 1 dose escalation study, a phase 2 tolerability and efficacy trial with low, intermediate, and high doses of idebenone was conducted. The results suggested that treatment with intermediate- and high-dose idebenone had beneficial effects on neurological symptoms. On the basis of these results, two phase 3 trials have been initiated, one in the United States with young ambulatory patients and one in Europe without limits on age and disease severity.