An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels

J Neurol. 2015 May;262(5):1344-53. doi: 10.1007/s00415-015-7719-2. Epub 2015 Apr 7.

Abstract

Friedreich ataxia (FRDA) is due to a triplet repeat expansion in FXN, resulting in deficiency of the mitochondrial protein frataxin. Resveratrol is a naturally occurring polyphenol, identified to increase frataxin expression in cellular and mouse models of FRDA and has anti-oxidant properties. This open-label, non-randomized trial evaluated the effect of two different doses of resveratrol on peripheral blood mononuclear cell (PBMC) frataxin levels over a 12-week period in individuals with FRDA. Secondary outcome measures included PMBC FXN mRNA, oxidative stress markers, and clinical measures of disease severity. Safety and tolerability were studied. Twenty-four participants completed the study; 12 received low-dose resveratrol (1 g daily) and 12 high-dose resveratrol (5 g daily). PBMC 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 neurologic function was evident in the high-dose group [change in Friedreich Ataxia Rating Scale -3.4 points, 95% CI (-6.6, -0.3), p = 0.036], but not the low-dose group. Significant improvements in audiologic and speech measures, and in the oxidative stress marker plasma F2-isoprostane were demonstrated in the high-dose group only. There were no improvements in cardiac measures or patient-reported outcome measures. No serious adverse events were recorded. Gastrointestinal side-effects were a common, dose-related adverse event. This open-label study shows no effect of resveratrol on frataxin levels in FRDA, but suggests that independent positive clinical and biologic effects of high-dose resveratrol may exist. Further assessment of efficacy is warranted in a randomized placebo-controlled trial.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Antioxidants / therapeutic use*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • F2-Isoprostanes / blood
  • Female
  • Fourier Analysis
  • Friedreich Ataxia / drug therapy*
  • Friedreich Ataxia / metabolism*
  • Humans
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Resveratrol
  • Stilbenes / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Antioxidants
  • F2-Isoprostanes
  • Iron-Binding Proteins
  • RNA, Messenger
  • Stilbenes
  • frataxin
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Resveratrol