The use of antioxidants in Friedreich’s ataxia treatment

Abstract

Friedreich’s ataxia is the most common recessive ataxia associated with life-threatening cardiomyopathy. It results from a loss of function of frataxin that ultimately leads to oxidative insult, particularly to neurons and cardiomyocytes. The disease is progressive, the oxidative insult being presumably subsequent to an abnormal iron/sulfur cluster synthesis that causes mitochondrial respiratory chain disease and impaired signalling of one antioxidant pathway. After a detailed in vitro study, idebenone, a short chain homologue of coenzyme Q₁₀ with potent antioxidant properties, was given to patients. The antioxidant had a dramatic and rapid effect on the cardiomyopathy in most patients. Although a subset of patients also report various improvements, implying that idebenone could have a broader spectrum of action including some neurological improvements, the antioxidant did not have noticeable effects on the ataxia. Several hypotheses on the mechanisms that could account for the contrasting effects of the antioxidant on clinical symptoms of Friedreich’s ataxia are discussed in this review. The considerable difficulties still being encountered in ascertaining the effect of antioxidants on the course of the neurological condition are also considered.

• cardiomyopathy
• idebenone
• mitochondria
• rare disease