State of the Art and History of Therapeutics in Ataxias

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.