Introduction: Friedreich ataxia (FRDA) is due to a triplet repeat expansion in the FXN gene, resulting in deficiency of the mitochondrial protein frataxin. Resveratrol is a plant-derived polyphenol. It increased frataxin expression in cellular and mouse models of FRDA, and has anti-oxidant properties.

Methods: This trial evaluated the effect of two different doses of resveratrol on lymphocyte frataxin levels over a 12-week period in individuals with FRDA. Secondary aims evaluated the effect on FXN mRNA, oxidative stress markers and clinical measures of disease severity. Safety and tolerability were studied.

Results: 24 participants completed the study; 12 received low-dose resveratrol (1g daily) and 12 high-dose resveratrol (5g daily). Lymphocyte frataxin levels did not change in either dosage group [low dose group change: 0.08 pg/μg protein (95% CI -0.05, 0.21, p=0.21); high dose group change: 0.03 pg/μg protein (95% CI -0.10, 0.15, p=0.62)]. Improvement in ataxia was evident in the high-dose group (change in International Cooperative Ataxia Rating Scale, ICARS -1.9 points, 95% CI -3.1, -0.8, p=0.004) but not the low-dose group (change in ICARS -0.3 points, 95% CI -3.2, 2.6, p=0.80). Significant improvements in hearing and speech were demonstrated in the high-dose group. A significant decrease in the oxidative stress marker plasma F2-isoprostanes occurred in the high-dose group. No serious adverse events were recorded. Gastrointestinal side effects were a common, dose-related adverse event.

Conclusions: This trial provides evidence for high-dose resveratrol as a potential disease-modifying therapy for FRDA. A placebo-controlled trial is required to assess its benefits further.