OBJECTIVES: Ataxia is a neurological disorder characterized by coordination loss, impacting movement, speech, and eye control, with a few effective treatment options. The systematic literature review (SLR) aimed to evaluate the efficacy of pharmacological interventions in ataxia.

METHODS: Key biomedical databases (Embase^® and Medline^®) and trial registries were searched from inception to May 2024 to identify the evidence meeting the prespecified eligibility criteria. The SLR was performed using the PRISMA-compliant two-review and quality control process.

RESULTS: Ten studies were identified (N=1347, mean age=39.4y, female=14.6%). Across these, idebenone and riluzole (2 studies each) were the most commonly assessed interventions, followed by one study each for amantadine hydrochloride, deferiprone, luvadaxistat, omaveloxolone, rovatirelin, and troriluzole. Four studies were conducted globally, two in the US and one study each in Japan, France, Italy, and Canada. Scale for the Assessment and Rating of Ataxia (SARA) (n=4) was most commonly used to assess the efficacy, followed by the Nine-hole peg test (9-HPT) (n=3), Friedreich ataxia–validated Activities of Daily Living (FA‐ADL) (n=2). One study each utilized the International Cooperative ARS, FARS, modified (m) FARS, and mFARS-neuro scales. Omaveloxolone was associated with a higher mean change from baseline on the 9-HPT scale at 48 weeks vs. placebo in patients with Friedreich's ataxia (−0.0014 vs. −0.0001) and showed improvement on mFARS (47% vs 27%) and FA-ADL (36% vs 20%). Riluzole was associated with improvements on the SARA scale compared to placebo at 12 months in patients with hereditary cerebellar ataxia (50% vs 11%). The remaining interventions did not demonstrate improvement on any of the scales compared to placebo.

CONCLUSIONS: Limited therapeutic options are available for ataxia, often focusing on symptomatic management rather than addressing the underlying cause. This SLR underscores a notable gap in treatments that directly target ataxia and highlights the potential pharmacological treatments in treating ataxia or slowing its progression.