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Author Notes:

Correspondence: Tetsuo Ashizawa; ashizawa@ufl.edu

Authors' Contributions: All authors have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; have been involved in drafting the manuscript or revising it critically for important intellectual content; and have given final approval of the version being submitted.

TA participated in designing and conceptualizing the study, collecting data, analyzing and interpreting the data, drafting the manuscript and revising the manuscript; He was the principal investigator for the entire research operation of the CRC-SCA.

See publication for full list of author contributions.

Acknowledgments: We thank local support groups and the National Ataxia Foundation Chapters.

We also thank following clinical research coordinators: Bettye Robinson and Rebecca McMurray (Emory University), Elizabeth Sullivan (University of Michigan), J McMore (Massachusetts General Hospital), Brian Jung (Johns Hopkins University), Vicky Staszak (University of Chicago), Sharone Trifkin, Tarshia Nulliah and Maria Casado (UCLA), Gigi Satris (UCSF), Diane Hutter (University of Minnesota), Jessica Shaw and Kelly Sullivan (University of South Florida), and Rebecca Beaulier and Phuong Deleyroll (University of Florida).

Disclosures: Ms. Figueroa, Dr. Schmahmann, Dr. Bushara, Dr. Mazzoni, Mr. Cuthbertson, Ms. Roberts Holbert and Dr. Ferguson report no disclosures.

Subjects:

Research Funding:

This study was supported by NIH grant NS068897 to TA.

Dr. Ashizawa was supported by NIH (RC1NS068897) for this work (2009-2012) and is receiving another NIH grant (R01NS083564) (2013-2018); He also receives research funding from the National Ataxia Foundation (2013) and the Muscular Dystrophy Association (2013-2015). He has been receiving royalty from Baylor College of Medicine (since 2001); He has received travel reimbursement from the Japanese Society of Neurology (2013), Cooperative Clinical Research Network–Friedreich Ataxia (2013), Muscular Dystrophy Foundation (2013), Central China University (with honorarium, 2012), Baylor College of Medicine (2012), Texas Neurological Society (2012), Unstable Microsatellites and Human Diseases (2011), Fudan University (with honorarium, 2011) and International Myotonic Dystrophy Consortium (2011).

Dr. Perlman received research grantS from Santhera Pharmaceuticals (2011), EDISON PHARMACEUTICALS (2012-13), FRIEDREICHS ATAXIA RESEARCH ALLIANCE (2002-2013), and National Ataxia Foundation (2013).

Dr. Gomez receives NIH grant R01NS033202 (2010-2015).

Dr. Wilmot is a member of the Data Safety Monitoring Board for Santhera Pharmaceuticals and has received support from the Cooperative Clinical Research Network–Friedreich Ataxia.

Dr. Ying has been supported by NIH grants R21 NS059830, R01 EY019347, R01 NS056307, R21 EY022150, and received other research support from the Brain Science Institute and 5RC1NS068897.

Dr. Zesiewicz received compensation from UCB Pharma, Teva and GE for Speaking activities, grants from Astellas Pharmaceuticals, Baxter, Friedreich’s Ataxia Research Alliance, Takeda, Edison Pharmaceuticals, and GlaxoSmithKline for the past yer.

See publication for full funding statement.

Keywords:

  • Spinocerebellar ataxia
  • Natural history
  • SARA
  • Progression rate

Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study

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Journal Title:

Orphanet Journal of Rare Diseases

Volume:

Volume 8, Number 177

Publisher:

, Pages None-

Type of Work:

Article | Final Publisher PDF

Abstract:

Background All spinocerebellar ataxias (SCAs) are rare diseases. SCA1, 2, 3 and 6 are the four most common SCAs, all caused by expanded polyglutamine-coding CAG repeats. Their pathomechanisms are becoming increasingly clear and well-designed clinical trials will be needed. Methods To characterize the clinical manifestations of spinocerebellar ataxia (SCA) 1, 2, 3 and 6 and their natural histories in the United States (US), we conducted a prospective multicenter study utilized a protocol identical to the European consortium study, using the Scale for the Assessment and Rating of Ataxia (SARA) score as the primary outcome, with follow-ups every 6 months up to 2 years. Results We enrolled 345 patients (60 SCA1, 75 SCA2, 138 SCA3 and 72 SCA6) at 12 US centers. SCA6 patients had a significantly later onset, and SCA2 patients showed greater upper-body ataxia than patients with the remaining SCAs. The annual increase of SARA score was greater in SCA1 patients (mean ± SE: 1.61 ± 0.41) than in SCA2 (0.71 ± 0.31), SCA3 (0.65 ± 0.24) and SCA6 (0.87 ± 0.28) patients (p = 0.049). The functional stage also worsened faster in SCA1 than in SCA2, 3 and 6 (p = 0.002). Conclusions The proportions of different SCA patients in US differ from those in the European consortium study, but as in the European patients, SCA1 progress faster than those with SCA2, 3 and 6. Later onset in SCA6 and greater upper body ataxia in SCA2 were noted. We conclude that progression rates of these SCAs were comparable between US and Europe cohorts, suggesting the feasibility of international collaborative clinical studies. Keywords: Spinocerebellar ataxia, Natural history, SARA, Progression rate

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© 2013 Ashizawa et al.; licensee BioMed Central Ltd

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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