Abstract
Introduction Tourette syndrome (TS) is a complex neurodevelopmental
disorder characterized by chronic motor and vocal tics. While consistently
effective treatment is lacking, evidence indicates that the modulation of
endocannabinoid system is potentially beneficial. Lu AG06466 (previously
ABX-1431) is a highly selective inhibitor of monoacylglycerol lipase, the
primary enzyme responsible for the degradation of the endocannabinoid ligand
2-arachidonoylglycerol. This exploratory study aimed to determine the effect of
Lu AG06466 versus placebo on tics and other symptoms in patients with TS.
Methods In this phase 1b cross-over study, 20 adult patients with TS on
standard-of-care medications were randomized to a single fasted dose of Lu
AG06466 (40 mg) or placebo in period 1, followed by the other treatment
in period 2. The effects on tics, premonitory urges, and psychiatric
comorbidities were evaluated using a variety of scaled approaches at different
time points before and after treatment.
Results All scales showed an overall trend of tic reduction, with two out
of three tic scales (including the Total Tic Score of the Yale Global Tic
Severity Score) showing a significant effect of a single dose of Lu AG06466
versus placebo at various timepoints. Treatment with Lu AG06466 resulted in a
significant reduction in premonitory urges versus placebo. Single doses of Lu
AG06466 were generally well-tolerated, and the most common adverse events were
headache, somnolence, and fatigue.
Conclusion In this exploratory trial, a single dose of Lu AG06466 showed
statistically significant positive effects on key measures of TS symptoms.
Key words
Tourette syndrome - endocannabinoid - monoacylglycerol lipase - Lu AG06466
