Research in context
Evidence before this study
We searched PubMed from inception to Nov 23, 2021, for the following terms without language restriction: “cerebellar ataxia”, “spinocerebellar ataxias (SCAs)”, “riluzole”, and “clinical trials”. We found two clinical trials with evidence of clinical improvement after riluzole treatment. The first, a pilot study, included 40 patients affected by genetic and other forms of ataxias with a treatment duration of 8 weeks (NCT00202397), and the second trial included 60 patients with different causes of inherited cerebellar ataxias and disease stages treated for 12 months (NCT01104649) .
Added value of this study
The ATRIL study assessed the safety and efficacy of riluzole in patients with spinocerebellar ataxia type 2. We enrolled a homogeneous cohort of patients with spinocerebellar ataxia type 2 recruited by the French network of rare neurogenetic diseases. This choice for replication was justified by three facts: patients with spinocerebellar ataxia type 2 are among those included in previous ataxia studies; spinocerebellar ataxia type 2 can present an amyotrophic lateral sclerosis-like phenotype, and riluzole is widely used to treat amyotrophic lateral sclerosis; and intermediate ATXN2 alleles (27–32 CAG repeats) are a risk factor for amyotrophic lateral sclerosis. In addition, we used pretrial cerebral MRI scans (cerebellum and brainstem volumes), added a quantitative measure of ataxia (the composite cerebellar functional severity score), and carefully analysed motor neuron involvement and quality-of-life measures. The ATRIL results showed no clinical or radiological improvement after riluzole treatment in patients with spinocerebellar ataxia type 2. However, we were able to measure significant volume loss over 12 months for specific brain regions in these patients.
Implications of all the available evidence
We report the absence of improvement of clinical or radiological outcomes under riluzole treatment, despite satisfactory treatment compliance and absence of serious adverse events. However, our longitudinal imaging results might provide valuable biomarkers for upcoming clinical trials.