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Erschienen in: Journal of Neurology 5/2015

01.05.2015 | Original Communication

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

verfasst von: 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

Erschienen in: Journal of Neurology | Ausgabe 5/2015

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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.
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Metadaten
Titel
An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels
verfasst von
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
Publikationsdatum
01.05.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 5/2015
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-015-7719-2

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