Abstract Details

Title ABX-1431, A First-in-Class Endocannabinoid Modulator, Improves Tics in Adult Patients with Tourette Syndrome

Topic Movement Disorders

Presentation(s) ES1 - (-)

Poster/Presentation
Number 002

Objective

Background TS is a neurodevelopmental condition characterized by motor and vocal tics with onset in childhood. ABX-1431 is a first-in-class, oral, highly selective inhibitor of the enzyme monoacylglycerol lipase (MGLL) that raises nervous system concentrations of the endocannabinoid 2-AG, which acts as an agonist on presynaptic central cannabinoid (CB1) receptors. Since 2-AG exerts feedback inhibition on neurotransmitter release, and MGLL in abundant in the basal ganglia, ABX-1431 may improve tics and comorbidities in TS.

Design/Methods 20 adult patients (16 men, 4 women, age 18-54) with moderate-severe TS were treated in a single-dose crossover study with 40 mg ABX-1431 or placebo. Endpoints were tic severity according to the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS), the Modified Rush Video-Based Tic Rating Scale (MRVS), and the self-assessment Adult Tic Questionnaire (ATQ), and premonitory urges according to the Premonitory Urge for Tics Scale (PUTS).

Results Patients displayed a placebo-adjusted ABX-1431-related tic improvement in the YGTSS-TTS at 8 hours (p=0.0384), with improvement in motor tics at 4 hours (p=0.0016) and 8 hours (p=0.0049), and a reduction in self-reported tic intensity (ATQ) at 4 hours (p=0.0005) and 8 hours (p=0.0008). A placebo-adjusted ABX-1431-related improvement in premonitory urges was observed at 4 hours (PUTS, p=0.0369), while no significant difference was observed with the MRVS. The most common adverse events were headache, somnolence, and fatigue, which resloved.

Conclusions Our data suggest that modulation of the endocannabinoid system by selective inhibition of MGLL improves tics in TS. ABX-1431 may provide a unique treatment profile for TS, and holds promise as a novel mechanism to treat movement disorders and neuropsychiatric conditions.

Authors/Disclosures
	No disclosure on file
Ewgeni Jakubovski	No disclosure on file
	No disclosure on file
	No disclosure on file
Chan Beals	Chan Beals has received personal compensation for serving as an employee of Autobahn Therapeutics.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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