Journal article
Progression of Friedreich ataxia: quantitative characterization over 5 years
Annals of clinical and translational neurology, Vol.3(9), pp.684-694
09/2016
DOI: 10.1002/acn3.332
PMCID: PMC5018581
PMID: 27648458
Abstract
Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes and changes to identify predictors of progression and generate power calculations for clinical trials.
Eight hundred and twelve subjects in a natural history study were evaluated annually across 12 sites using the Friedreich Ataxia Rating Scale (FARS), 9-Hole Peg Test, Timed 25-Foot Walk, visual acuity tests, self-reported surveys and disability scales. Cross-sectional outcomes were assessed from recent visits, and longitudinal changes were gaged over 5 years from baseline.
Cross-sectional outcomes correlated with measures of disease severity. Age, genetic severity (guanine-adenine-adenine [GAA] repeat length), and testing site predicted performance. Serial progression was relatively linear using FARS and composite measures of performance, while individual performance outcomes were nonlinear over time. Age strongly predicted change from baseline until removing the effects of baseline FARS scores, when GAA becomes a more important factor. Progression is fastest in younger subjects and subjects with longer GAA repeats. Improved coefficients of variation show that progression results are more reproducible over longer assessment durations.
While age predicted progression speed in simple analyses and may provide an effective way to stratify cohorts, separating the effects of age and genetic severity is difficult. Controlling for baseline severity, GAA is the major determinant of progression rate in FRDA. Clinical trials will benefit from enrollment of younger subjects, and sample size requirements will shrink with longer assessment periods. These findings should prove useful in devising gene therapy trials in the near future.
Details
- Title: Subtitle
- Progression of Friedreich ataxia: quantitative characterization over 5 years
- Creators
- Maya Patel - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaCharles J Isaacs - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaLauren Seyer - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaKarlla Brigatti - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaSarah Gelbard - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaCassandra Strawser - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaDebbie Foerster - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaJulianna Shinnick - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaKimberly Schadt - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaEppie M Yiu - Bruce Lefroy Centre Murdoch Childrens Research Institute Parkville Victoria AustraliaMartin B Delatycki - Bruce Lefroy Centre Murdoch Childrens Research Institute Parkville Victoria AustraliaSusan Perlman - Department of Neurology David Geffen School of Medicine University of California Los Angeles Los Angeles CaliforniaGeorge R Wilmot - Department of Neurology Emory University Atlanta GeorgiaTheresa Zesiewicz - Department of Neurology University of South Florida and the James A. Haley Veterans' Administration Tampa FloridaKatherine Mathews - Department of Neurology and Pediatrics University of Iowa Iowa City IowaChristopher M Gomez - Department of Neurology University of Chicago Chicago IllinoisGrace Yoon - Division of Clinical and Metabolic Genetics The Hospital for Sick Children University of Toronto Toronto Ontario CanadaSub H Subramony - Department of Neurology University of Florida Gainesville FloridaAlicia Brocht - Center for Human Experimental Therapeutics University of Rochester Rochester New YorkJennifer Farmer - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia PennsylvaniaDavid R Lynch - Departments of Pediatrics and Neurology The Children's Hospital of Philadelphia Philadelphia Pennsylvania; Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.3(9), pp.684-694
- DOI
- 10.1002/acn3.332
- PMID
- 27648458
- PMCID
- PMC5018581
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Publisher
- United States
- Grant note
- DOI: 10.13039/100002108, name: Friedreich's Ataxia Research Alliance
- Language
- English
- Date published
- 09/2016
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984070674902771
Metrics
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