N-Acetyl-leucine in progressive CACNA1A ataxia: A case series.

Background: CACNA1A-related disorders are rare and progressive; to date, there is no approved treatment. Trials with N-acetyl-leucine (NAL) demonstrated efficacy in disorders featuring ataxia, cognitive impairment, and epilepsy. Accordingly, we hypothesized that NAL may be effective in CACNA1A-associated disorders.

Cases: Four patients (1 boy, age 15 years, 3 girls, age 5, 9, and 14) received NAL as individualized off-label treatment and were assessed using the SARA Score, SCAFI and CGI-I. In all children NAL resulted in rapid improvement of ataxia, (gait, balance, fine motor and speech - mean SARA improvement at first follow-up: 3.25 points). Improvement was sustained up to 3 years (mean long-term SARA improvement: 5.13 points). SCAFI and CGI-I showed similar improvement. NAL was well-tolerated, without adverse reactions.

Conclusions: N-acetyl-leucine is a novel potential treatment for a so far untreatable rare disease spectrum of CACNA1A-disorders. The sustained benefit may reflect neuroprotective effects seen in other populations. Clinical trials are needed to control the results.