An open label clinical pilot study of resveratrol as a treatment for Friedreich ataxia.

Friedreich ataxia (FRDA), the most common hereditary ataxia, is due to a GAA triplet repeat expansion in intron 1 of the FXN gene in about 98% of affected individuals, resulting in deficiency of the mitochondrial protein frataxin. There is no treatment proven to alter its natural history. Resveratrol is a plant-derived compound. It was identified to increase frataxin expression in cellular and mouse models of FRDA, and is proposed to have anti-oxidant and neuroprotective properties. This is an open-label sequential clinical pilot study evaluating the effect of two different doses of resveratrol on lymphocyte frataxin levels over a 12-week period. Inclusion criteria include: (i) age >18 years; (ii) homozygosity for the GAA repeat expansion in FXN; (iii) at least minimum clinical evidence of ataxia; and (iv) adequate end organ function. A total of 28 participants will be enrolled (14 participants 1 g resveratrol daily; 14 participants 5 g resveratrol daily). The primary aim is to evaluate the effect of two doses of resveratrol on lymphocyte frataxin levels at 12 weeks compared to baseline. A number secondary aims will evaluate the effect of resveratrol on FXN mRNA expression, markers of oxidative stress, clinical measures of FRDA, and echocardiography findings at 12 weeks compared to baseline. The safety of resveratrol, and pharmacokinetic data will also be evaluated. This trial is expected to reach completion in August 2012. Preliminary data will be presented. Resveratrol shows promise as a treatment for FRDA. This clinical pilot trial will evaluate its effect on biomarker and clinical measures over a 12-week period. If evidence of biological effect is seen, a placebo-controlled study will be undertaken.