TY - CHAP
T1 - State of the Art and History of Therapeutics in Ataxias
AU - Kingsbury, Chase
AU - Ghanekar, Shaila
AU - Huang, Yangxin
AU - Zhao, Yayi
AU - Ashizawa, Tetsuo
AU - Kuo, Sheng Han
AU - Gooch, Clifton L.
AU - Zesiewicz, Theresa A.
N1 - Funding Information:
For FRDA, the government agencies that funded the most clinical trials were the NIH, the German Research Foundation, the Italian Agency for Pharmaceutics, and the Murdoch Children’s Research Institute, Australia (also private funding for the latter). The most active private foundations were the Friedreich’s Ataxia Research Alliance (FARA) and Ataxia UK, while active industries included Santhera Pharmaceuticals, Takeda Pharmaceuticals, Retrotope Inc., Reata Pharmaceuticals, Minoryx, and Larimar therapeutics. For SCA, government agencies that funded the most clinical trials were NIH, Hospital de Clinicas de Porto Alegre (Brazil), Cuban Ministry of Public Health, and Ministry of Science and Technology, Taiwan; the top private foundations included Deutsche Heredo-Ataxia Gesellschaft, the National Ataxia Foundation (NAF), and the Bobby Allison Research Foundation. The industry that funded SCA research was Biohaven Pharmaceuticals, and private universities/hospitals were Chang Gung Medical Research Program in Taiwan and Columbia University, New York City, USA.
Publisher Copyright:
© 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.
PY - 2023
Y1 - 2023
N2 - Research into novel therapeutics suggests that treatment of cerebellar ataxia may be attainable in the future. Recently, omaveloxolone, an NRF2 activator, has become the first treatment approved by the United States Food and Drug Administration (FDA) for Friedreich’s ataxia (FRDA). We performed a systematic review of clinical trials to better understand the challenges hindering the development of successful therapies, and to identify potential shortcomings in the clinical pipeline. Clinical trials published in English were identified in several worldwide scientific databases. Trials were prospective, either single- or double-blinded (including blinded video assessments for neuromodulation trials), with a change in the severity of ataxia symptoms as the primary measure. Eighty-nine controlled clinical trials were accepted for extraction, including 3625 patients. The most common therapeutic modality over the past 50 years was pharmaceutical (idebenone). SCA3 had the highest number of patients in clinical trials in spinocerebellar ataxia (SCA). Only 9% of clinical trials reported race/ethnicity, which was predominantly white in all ataxias combined (approximately 81%). The majority of clinical trials in FRDA were performed in North America and Europe, while for SCAs, most were performed in the USA, Europe, Japan, Taiwan, Brazil, and Cuba. Clinical trials in cerebellar ataxia reported significantly more funding sources in the last 20 years than from 1980 to 1999 (p = 0.016). Future ataxia research should be more inclusive and diverse while focusing on novel therapeutics.
AB - Research into novel therapeutics suggests that treatment of cerebellar ataxia may be attainable in the future. Recently, omaveloxolone, an NRF2 activator, has become the first treatment approved by the United States Food and Drug Administration (FDA) for Friedreich’s ataxia (FRDA). We performed a systematic review of clinical trials to better understand the challenges hindering the development of successful therapies, and to identify potential shortcomings in the clinical pipeline. Clinical trials published in English were identified in several worldwide scientific databases. Trials were prospective, either single- or double-blinded (including blinded video assessments for neuromodulation trials), with a change in the severity of ataxia symptoms as the primary measure. Eighty-nine controlled clinical trials were accepted for extraction, including 3625 patients. The most common therapeutic modality over the past 50 years was pharmaceutical (idebenone). SCA3 had the highest number of patients in clinical trials in spinocerebellar ataxia (SCA). Only 9% of clinical trials reported race/ethnicity, which was predominantly white in all ataxias combined (approximately 81%). The majority of clinical trials in FRDA were performed in North America and Europe, while for SCAs, most were performed in the USA, Europe, Japan, Taiwan, Brazil, and Cuba. Clinical trials in cerebellar ataxia reported significantly more funding sources in the last 20 years than from 1980 to 1999 (p = 0.016). Future ataxia research should be more inclusive and diverse while focusing on novel therapeutics.
KW - Cerebellar ataxia
KW - Clinical trials
KW - Friedreich’s ataxia
KW - Gender
KW - Spinocerebellar
UR - http://www.scopus.com/inward/record.url?scp=85161413839&partnerID=8YFLogxK
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U2 - 10.1007/978-3-031-24345-5_29
DO - 10.1007/978-3-031-24345-5_29
M3 - Chapter
AN - SCOPUS:85161413839
T3 - Contemporary Clinical Neuroscience
SP - 691
EP - 722
BT - Contemporary Clinical Neuroscience
PB - Springer
ER -