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

TitleAn open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels
Authors
Issue Date2015
PublisherSpringer Verlag. The Journal's web site is located at http://www.springer.com/medicine/neurology/journal/415
Citation
Journal of Neurology, 2015, v. 262 n. 5, p. 1344-1353 How to Cite?
AbstractFriedreich 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.
Persistent Identifierhttp://hdl.handle.net/10722/211042
ISSN
2015 Impact Factor: 3.408
2015 SCImago Journal Rankings: 1.429

 

DC FieldValueLanguage
dc.contributor.authorYiu, EM-
dc.contributor.authorTai, G-
dc.contributor.authorPeverill, RE-
dc.contributor.authorLee, KJ-
dc.contributor.authorCroft, KD-
dc.contributor.authorMori, TA-
dc.contributor.authorScheiber-Mojdehkar, B-
dc.contributor.authorSturm, B-
dc.contributor.authorPraschberger, M-
dc.contributor.authorVogel, AP-
dc.contributor.authorLee, CYJ-
dc.date.accessioned2015-07-03T07:59:36Z-
dc.date.available2015-07-03T07:59:36Z-
dc.date.issued2015-
dc.identifier.citationJournal of Neurology, 2015, v. 262 n. 5, p. 1344-1353-
dc.identifier.issn0340-5354-
dc.identifier.urihttp://hdl.handle.net/10722/211042-
dc.description.abstractFriedreich 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.-
dc.languageeng-
dc.publisherSpringer Verlag. The Journal's web site is located at http://www.springer.com/medicine/neurology/journal/415-
dc.relation.ispartofJournal of Neurology-
dc.rightsThe final publication is available at Springer via http://dx.doi.org/10.1007/s00415-015-7719-2-
dc.titleAn open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels-
dc.typeArticle-
dc.identifier.emailLee, CYJ: jettylee@hku.hk-
dc.identifier.authorityLee, CYJ=rp01511-
dc.identifier.doi10.1007/s00415-015-7719-2-
dc.identifier.pmid25845763-
dc.identifier.hkuros243248-
dc.identifier.volume262-
dc.identifier.issue5-
dc.identifier.spage1344-
dc.identifier.epage1353-
dc.publisher.placeGermany-

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