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article, pubmed, google, scholar, ataxia, cas, research, friedreich, resveratrol, frataxin, australia, reports, disclosures, clinical, delatycki, study, central, friedreichs, lee, vic, neurology, nhmrc, change, highdose, corben, measures, rating, scale, patients, support, parkville, department, content, trial, levels, yiu, vogel, protein, disease, group, res, cancer, university, privacy, cookies, journal, effect, tai, peverill, scheibermojdehkar,

Topics {✒️}

month download article/chapter dose-related adverse event randomized placebo-controlled trial oxidative stress markers double-blind pilot study patient-reported outcome measures high-dose group change high-dose group [change open-label study shows full article pdf isocratic lc-ms/ms mitochondrial protein frataxin clinical trial design low-dose group triplet repeat expansion open-label trial oxidative stress high-dose group privacy choices/manage cookies ataxia research alliance received salary support functional genomic analysis selected cardiovascular biomarkers healthy human subjects randomized trial evaluated related subjects monash medical centre national ataxia foundation independent positive clinical frataxin protein levels growth factor axis early career fellowship genetic health research fxn gene mutation high-dose resveratrol 12 high-dose resveratrol hubbard bp 08 pg/μg protein 03 pg/μg protein steady-state pharmacokinetics repeat dose study cancer prev res ataxia impact scale friedreich ataxia patients increase frataxin expression ataxia neuropharmacology committee peripheral blood cells barbara scheiber-mojdehkar neurologic rating scale article journal

Questions {❓}

• Fahey MC, Corben L, Collins V, Churchyard AJ, Delatycki MB (2007) How is disease progress in Friedreich’s ataxia best measured?
• Vang O, Ahmad N, Baile CA, Baur JA, Brown K, Csiszar A, Das DK, Delmas D, Gottfried C, Lin HY, Ma QY, Mukhopadhyay P, Nalini N, Pezzuto JM, Richard T, Shukla Y, Surh YJ, Szekeres T, Szkudelski T, Walle T, Wu JM (2011) What is new for an old molecule?

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         headline:An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels
         description: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.
         datePublished:2015-04-07T00:00:00Z
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            Clinical trial
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            Neuroradiology
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      headline:An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels
      description: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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         Friedreich ataxia
         Clinical trial
         Resveratrol
         Oxidative stress
         Mitochondrial disorder
         Neurology
         Neurosciences
         Neuroradiology
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      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
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      name:Department of Paediatrics, The University of Melbourne, Parkville, Australia
      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Monash Cardiovascular Research Centre, MonashHEART and Monash University Department of Medicine, Monash Medical Centre, Clayton, Australia
      name:Department of Paediatrics, The University of Melbourne, Parkville, Australia
      name:Clinical Epidemiology and Biostatistics Unit, Murdoch Childrens Research Institute, Parkville, Australia
      name:School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
      name:School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
      name:Department of Medical Chemistry, Medical University of Vienna, Vienna, Austria
      name:Department of Medical Chemistry, Medical University of Vienna, Vienna, Austria
      name:Department of Medical Chemistry, Medical University of Vienna, Vienna, Austria
      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Department of Audiology and Speech Pathology, The University of Melbourne, Parkville, Australia
      name:Department of Audiology and Speech Pathology, The University of Melbourne, Parkville, Australia
      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Department of Paediatrics, The University of Melbourne, Parkville, Australia
      name:Cell and Gene Therapy, Murdoch Childrens Research Institute, Parkville, Australia
      name:Australian Wine Research Institute, Adelaide, Australia
      name:School of Biological Sciences, The University of Hong Kong, Hong Kong, China
      name:Department of Neurology, Monash Health, Clayton, Australia
      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Department of Paediatrics, The University of Melbourne, Parkville, Australia
      name:Department of Neurology, Royal Children’s Hospital Melbourne, Parkville, Australia
      name:Department of Paediatrics, The University of Melbourne, Parkville, Australia
      name:Neurosciences Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Department of Paediatrics, The University of Melbourne, Parkville, Australia
      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Australia
      name:Department of Paediatrics, The University of Melbourne, Parkville, Australia
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