A Phase 2 clinical trial evaluating the efficacy and safety of L-arginine in treating Spinocerebellar Ataxia type 6 (SCA6) has shown promising trends, but failed to reach statistical significance. The multicenter, randomized, double-blind, placebo-controlled study, conducted across five institutions in Japan, suggests that L-arginine may offer some therapeutic benefits for patients with this debilitating neurodegenerative disorder.
The research was led by Specially Appointed Associate Professor Tomohiko Ishihara and Professor Osamu Onodera at Niigata University, along with Professor Yoshitaka Nagai at Kindai University. Their work explored L-arginine's potential to inhibit polyglutamine (polyQ) protein aggregation, a hallmark of several hereditary spinocerebellar ataxias.
Trial Design and Patient Population
The trial (AJA030-002, jRCT2031200135) enrolled 40 patients with SCA6, a subtype of spinocerebellar ataxia characterized by a relatively high prevalence and uniform symptom presentation in Japan. Participants were randomly assigned to receive either L-arginine or a placebo over a 48-week period. The primary aim of this exploratory Phase 2 trial was to assess the safety and preliminary efficacy of L-arginine in this patient population.
Efficacy and Safety Outcomes
The study assessed treatment efficacy using the Scale for the Assessment and Rating of Ataxia (SARA), a standardized tool for evaluating ataxia severity. After 48 weeks, the L-arginine group demonstrated an average improvement of 0.96 ± 0.55 points in SARA scores, indicating a mild reduction in ataxia symptoms. In contrast, the placebo group experienced a mean worsening of 0.56 ± 0.55 points in SARA scores. This translates to an approximate 1.5-point treatment effect over one year. However, the observed difference between the two groups did not reach statistical significance (p=0.0582).
Regarding safety, two serious adverse events potentially associated with L-arginine were reported. These included one case of pneumonia that resulted in fatality and one case of liver impairment that resolved.
Implications and Future Directions
While the study suggests that L-arginine may offer certain therapeutic benefits for patients with SCA6, the lack of statistical significance necessitates larger and more robust Phase 3 trials to definitively establish efficacy. According to the researchers, such trials would provide more reliable evidence for the use of L-arginine as a treatment for spinocerebellar ataxia and may clarify its long-term safety profile in this population.
Spinocerebellar ataxias are a group of neurodegenerative disorders affecting the cerebellum, leading to difficulties with balance, coordination, and speech. In Japan, approximately 30,000 people are affected by SCA, with one-third of cases being hereditary. If L-arginine proves effective in a larger cohort, it could become an important therapeutic option, addressing an unmet need in managing this progressive neurodegenerative disorder.
