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

• Type of Material: Article
• Authors: Tetsuo Ashizawa, University of Florida; Karla P Figueroa, University of Utah; Susan L Perlman, University of California; Christopher M Gomez, University of Chicago; George (Chip) Wilmot, Emory University; Jeremy D Schmahmann, Harvard University; Sarah H Ying, Johns Hopkins University; Theresa A Zesiewicz, University of South Florida; Henry L Paulson, University of Michigan; Vikram G Shakkottai, University of Michigan; Khalaf O Bushara, University of Minnesota; Sheng-Han Kuo, Columbia University; Michael D Geschwind, University of California; Guangbin Xia, University of Florida; Pietro Mazzoni, Columbia University; Jeffrey P Krischer, University of South Florida; David Cuthbertson, University of South Florida; Amy Roberts Holbert, University of South Florida; John H Ferguson, National Center for Advancing Translational Sciences; Stefan M Pulst, University of Utah; SH Subramony, University of Florida
• Language: English
• Date: 2013-11-13
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Ashizawa et al.; licensee BioMed Central Ltd
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.ojrd.com/content/8/1/177
• Title of Journal or Parent Work: Orphanet Journal of Rare Diseases
• ISSN: 1750-1172
• Volume: 8
• Issue: 177
• Grant/Funding Information: Dr. Perlman received research grantS from Santhera Pharmaceuticals (2011), EDISON PHARMACEUTICALS (2012-13), FRIEDREICHS ATAXIA RESEARCH ALLIANCE (2002-2013), and National Ataxia Foundation (2013).; See publication for full funding statement.; 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. 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.; 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. Gomez receives NIH grant R01NS033202 (2010-2015).; This study was supported by NIH grant NS068897 to TA.
• Keywords: Progression rate; Spinocerebellar ataxia; Natural history; SARA
• Research Categories: Biology, Neuroscience; Health Sciences, Radiology

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