Journal of Neurology

, Volume 262, Issue 5, pp 1344–1353 | Cite as

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

  • Eppie M. Yiu
  • Geneieve Tai
  • Roger E. Peverill
  • Katherine J. Lee
  • Kevin D. Croft
  • Trevor A. Mori
  • Barbara Scheiber-Mojdehkar
  • Brigitte Sturm
  • Monika Praschberger
  • Adam P. Vogel
  • Gary Rance
  • Sarah E. M. Stephenson
  • Joseph P. Sarsero
  • Creina Stockley
  • Chung-Yung J. Lee
  • Andrew Churchyard
  • Marguerite V. Evans-Galea
  • Monique M. Ryan
  • Paul J. Lockhart
  • Louise A. Corben
  • Martin B. Delatycki
Original Communication

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.

Keywords

Friedreich ataxia Clinical trial Resveratrol Oxidative stress Mitochondrial disorder 

Supplementary material

415_2015_7719_MOESM1_ESM.pdf (95 kb)
Supplementary material 1 (PDF 95 kb)
415_2015_7719_MOESM2_ESM.docx (55 kb)
Supplementary material 2 (DOCX 55 kb)
415_2015_7719_MOESM3_ESM.pdf (87 kb)
Supplementary material 3 (PDF 87 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Eppie M. Yiu
    • 1
    • 2
    • 3
  • Geneieve Tai
    • 1
  • Roger E. Peverill
    • 4
  • Katherine J. Lee
    • 3
    • 5
  • Kevin D. Croft
    • 6
  • Trevor A. Mori
    • 6
  • Barbara Scheiber-Mojdehkar
    • 7
  • Brigitte Sturm
    • 7
  • Monika Praschberger
    • 7
  • Adam P. Vogel
    • 1
    • 8
  • Gary Rance
    • 8
  • Sarah E. M. Stephenson
    • 1
    • 3
  • Joseph P. Sarsero
    • 9
  • Creina Stockley
    • 10
  • Chung-Yung J. Lee
    • 11
  • Andrew Churchyard
    • 12
  • Marguerite V. Evans-Galea
    • 1
    • 3
  • Monique M. Ryan
    • 2
    • 3
    • 13
  • Paul J. Lockhart
    • 1
    • 3
  • Louise A. Corben
    • 1
  • Martin B. Delatycki
    • 1
    • 3
    • 14
  1. 1.Bruce Lefroy Centre for Genetic Health ResearchMurdoch Childrens Research InstituteParkvilleAustralia
  2. 2.Department of NeurologyRoyal Children’s Hospital MelbourneParkvilleAustralia
  3. 3.Department of PaediatricsThe University of MelbourneParkvilleAustralia
  4. 4.Monash Cardiovascular Research CentreMonashHEART and Monash University Department of Medicine, Monash Medical CentreClaytonAustralia
  5. 5.Clinical Epidemiology and Biostatistics UnitMurdoch Childrens Research InstituteParkvilleAustralia
  6. 6.School of Medicine and PharmacologyUniversity of Western AustraliaPerthAustralia
  7. 7.Department of Medical ChemistryMedical University of ViennaViennaAustria
  8. 8.Department of Audiology and Speech PathologyThe University of MelbourneParkvilleAustralia
  9. 9.Cell and Gene TherapyMurdoch Childrens Research InstituteParkvilleAustralia
  10. 10.Australian Wine Research InstituteAdelaideAustralia
  11. 11.School of Biological SciencesThe University of Hong KongHong KongChina
  12. 12.Department of NeurologyMonash HealthClaytonAustralia
  13. 13.Neurosciences ResearchMurdoch Childrens Research InstituteParkvilleAustralia
  14. 14.Department of Clinical GeneticsAustin HealthHeidelbergAustralia

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