Spinocerebellar Ataxia Type 2 Treatment: Is Riluzole Effective?

An elderly lonely woman sitting by a window, looking out.
Researchers sought to test riluzole, a medication used to treat amyotrophic lateral sclerosis, in spinocerebellar ataxia type 2, a single genetic disease.

A randomized trial found that riluzole did not improve clinical or radiological outcomes among patients with spinocerebellar ataxia type 2 (SCA2). These findings were published in The Lancet Neurology.

SCA2 is one of seven subgroups of inherited, progressive neurologic diseases which typically onset during midlife. To date, no disease-modifying treatments have been found for SCA, however, 2 trials found some beneficial outcomes from therapy with riluzole, which is widely used to treat amyotrophic lateral sclerosis.

This multicenter, double-blind, randomized, placebo-controlled trial (ATRIL; ClinicalTrials.gov Identifier: NCT03347344) recruited patients from eight centers in France between 2018 and 2019. Patients (N=45) with SCA2 who had 33 or more CAG repeats in the affected gene, with disease onset before 50 years of age, and a scale for the assessment and rating of ataxia (SARA) score of 5-26 were randomized in a 1:1 ratio to receive 50 mg oral riluzole (n=22) or placebo (n=23) twice daily for 12 months. Safety and efficacy were evaluated.

Patients treated with riluzole and individuals treated with placebo were 36% and 65% women, aged median 42 (interquartile range [IQR], 36-57) and 49 (IQR, 40-56) years, experienced disease onset at 32 (IQR, 25-43) and 38 (IQR, 29-44) years of age, and SARA scores were 15.3 (IQR, 10.0-20.5) and 12.5 (IQR, 9.0-16.0) points, respectively.

The primary outcome of a 1-point improvement in SARA score was observed among 32% of riluzole and 39% of placebo recipients (P =.75). Overall, both the intervention (change in SARA, 0.5; 95% CI, -1.5 to 1.5) and placebo (change in SARA, 0.3; 95% CI, -1.0 to 2.5) cohorts exhibited a nonsignificant worsening of symptoms.

The only observed group difference was that patients treated with riluzole exhibited a significant worsening of the composite cerebellar functional severity score (CCFS) (change in CCFS, 0.055; 95% CI, 0.014-0.086) and the control group individuals did not (change in CCFS, 0.004; 95% CI, -0.040 to 0.020; P =.0050).

All participants tended to report poorer quality of life measurements, although no group differences were observed.

Patients treated with riluzole reported numerically fewer adverse events (73% vs 83%; P =.49) and serious adverse events (0% vs 17%; P =.10).

This study was limited by the absence of neurofilament measurement, oculomotor recording, or wearable sensor assessment.

“Riluzole did not improve clinical or radiological outcomes in these patients,” the researchers concluded. However, they suggest their findings can offer insight into SCA2 progression, which may help with the future design of clinical trials.

Reference

Coarelli G, Heinzmann A, Ewenczyk C, et al. Safety and efficacy of riluzole in spinocerebellar ataxia type 2 in France (ATRIL): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. Published online January 18, 2022. doi:10.1016/S1474-4422(21)00457-9