The Natural History of Spinocerebellar Ataxia Type 3 in Mainland China: A 2-Year Cohort Study

• Type of Material: Article
• Authors: Yun Peng, Central South University; Linliu Peng, Central South University; Zhao Chen, Central South University; Huirong Peng, Central South University; Puzhi Wang, Central South University; Youming Zhang, Central South University; Yangping Li, Emory University; Chunrong Wang, Central South University; Yuting Shi, Central South University; Xuan Hou, Central South University; Zhe Long, Central South University; Hongyu Yuan, Central South University; Na Wan, Central South University; Linlin Wan, Central South University; Keqin Xu, Central South University; Lijing Lei, Central South University; Shang Wang, Central South University; Lang He, Central South University; Yue Xie, Central South University; Yiqing Gong, Central South University; Qi Deng, Central South University; Guangdong Zou, Central South University; Zhichao Tang, Central South University; Lu Shen, Central South University; Kun Xia, Central South University; Rong Qiu, Central South University; Thomas Klockgether, University of Bonn; Beisha Tang, Central South University; Hong Jiang, Central South University
• Language: English
• Date: 2022-07-05
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Peng, Peng, Chen, Peng, Wang, Zhang, Li, Wang, Shi, Hou, Long, Yuan, Wan, Wan, Xu, Lei, Wang, He, Xie, Gong, Deng, Zou, Tang, Shen, Xia, Qiu, Klockgether, Tang and Jiang.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fnagi.2022.917126
• Title of Journal or Parent Work: FRONTIERS IN AGING NEUROSCIENCE
• Volume: 14
• Start Page: 917126
• End Page: 917126
• Grant/Funding Information: This study was funded by the National Key Research and Development Program of China (Grant No. 2021YFA0805200 to HJ), the National Natural Science Foundation of China (Grant Nos. 81771231, 81974176, and 82171254 to HJ; Grant No. 81901169 to ZC; Grant No. 81901305 to CW), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (Grant No. 2020JJ1008 to HJ), the Science and Technology Innovation Group of Hunan Province (Grant No. 2020RC4043 to HJ), the Scientific Research Foundation of Health Commission of Hunan Province (Grant No. B2019183 to HJ), the Key Research and Development Program of Hunan Province (Grant Nos. 2020SK2064 and 2018SK2092 to HJ), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to HJ, the Natural Science Foundation of Hunan Province (Grant No. 2021JJ40974 to ZC and Grant No. 2020JJ5925 to CW), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, Grant No. 2020LNJJ12 and Grant No. XYYYJSTG-05 to HJ), the Youth Foundation of Xiangya Hospital (Grant No. 2018Q05 to CW), and the Clinical and Rehabilitation Funds of Peking University Weiming Biotech Group (Grant No. xywm2015I10 to HJ).
• Keywords: DISEASE PROGRESSION; Machado-Joseph disease (MJD); Life Sciences & Biomedicine; natural history; Neurosciences; ATXN3; Neurosciences & Neurology; Science & Technology; disease progression; spinocerebellar ataxia type 3; Geriatrics & Gerontology
• Research Categories: Health Sciences, Radiology; Health Sciences, Pathology

Abstract

Objective: The natural history of spinocerebellar ataxia type 3 (SCA3) has been reported in several populations and shows heterogeneity in progression rate and affecting factors. However, it remains unexplored in the population of Mainland China. This study aimed to identify the disease progression rate and its potential affecting factors in patients with SCA3 in Mainland China. Participants and Methods: We enrolled patients with genetically confirmed SCA3 in Mainland China. Patients were seen at three visits, i.e., baseline, 1 year, and 2 years. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA), and the secondary outcomes were the Inventory of Non-Ataxia Signs (INAS) as well as the SCA Functional Index (SCAFI). Results: Between 1 October 2015, and 30 September 2016, we enrolled 263 patients with SCA3. We analyzed 247 patients with at least one follow-up visit. The annual progression rate of SARA was 1.49 points per year (SE 0.08, 95% confidence interval [CI] 1.33–1.65, p < 0.0001). The annual progression rates of INAS and SCAFI were 0.56 points per year (SE 0.05, 95% CI 0.47–0.66, p < 0.001) and −0.30 points per year (SE 0.01, 95% CI −0.33∼-0.28, p < 0.001), respectively. Faster progression in SARA was associated with longer length of the expanded allele of ATXN3 (p < 0.0001); faster progression in INAS was associated with lower INAS at baseline (p < 0.0001); faster decline in SCAFI was associated with shorter length of the normal allele of ATXN3 (p = 0.036) and higher SCAFI at baseline (p < 0.0001). Conclusion: Our results provide quantitative data on the disease progression of patients with SCA3 in Mainland China and its corresponding affecting factors, which could facilitate the sample size calculation and patient stratification in future clinical trials. Trial Registration: This study was registered with Chictr.org on 15 September 2015, number ChiCTR-OOC-15007124.