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Novel Endocannabinoid Modulator Improves Tics in Tourette's

— In small study, total number, intensity decreased with minimal side effects, although no change for vocal tics

Ƶ MedicalToday

LOS ANGELES -- A novel cannabinoid agent improved symptoms in Tourette syndrome in a double-blind trial, researchers reported here.

ABX-1431 -- an investigational, first-in-class endocannabinoid modulator -- showed significant improvement in Tourette syndrome tics measured by the total score on the Yale Global Tic Severity Scale after 4 and 8 hours. Of the 19 patients included in the crossover study, four had a more than 25% decrease in total tics versus only one patient on placebo.

Motor tics were also significantly decreased after 4 hours, with a sustained improvement through 8 hours, according to the study by Kirsten Müller-Vahl, MD, of Hannover Medical School in Germany, and colleagues. Vocal tics remained unchanged with the treatment, however.

The late-breaking abstract presented at an emerging science session at the American Academy of Neurology annual meeting also reported a significant improvement in the intensity of tics, self-reported with the Adult Tic Questionnaire. Nearly half of participants had over a 50% decrease in tic intensity after 4 and 8 hours versus none of the participants on placebo.

Although there was a trend towards benefit measured on the Modified Rush Video-Based Tic Rating Scale, this was not statistically significant, the researchers noted. However, there was a benefit seen in premonitory urges after 4 hours, measured on the Premonitory Urge for Tics Scale.

The team explained that the treatment works as a selective monoacylglycerol lipase inhibitor to prevent the degradation of endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid. The novel modulator then activates cannabinoid receptor CB1 by increasing 2-AG signaling in active synapses to allow greater efficacy, as opposed to CB1 sole activity in the basal ganglia.

For the study, patients received a 40 mg single dose of the treatment with continuation of other medications other than medical cannabis or cannabinoids. Exclusion criteria included unstable organ function and a history or suicidality or psychosis.

Although ABX-1431 was generally well tolerated, with no serious events reported in the small study, the most common adverse events reported were headache, somnolence, and fatigue.

"I think it's a very interesting first step -- it's always exciting to have a new class of medications for a disorder, and certainly Tourette's," commented Michael Pourfar, MD, of NYU Langone Health in New York City, who was not involved with the study. "We treat [Tourette's] mainly with two classes of medicines -- alpha-2 adrenergic agonists and dopamine blockers -- the later being more effective, but having a fair number of potentially concerning side effects. So anything that is effective and well tolerated would certainly be welcome."

He explained to Ƶ that these findings "build on some of the sort of small, anecdotal, and studied reports of marijuana being helpful for Tourette's, which I've certainly seen in some of my patients, and optimistically I think it's intriguing. It's a very small, very short study and it's hard to make any broad, long-term claims about, but these are how we sort of cautiously move forward with the first-in-class medicines."

Study co-author Ewgeni Jakubovski, also of Hannover Medical School, told Ƶ that the group plans to build upon these positive findings with a larger follow-up study across multiple centers testing more continuous doses, which is already in preparation.

"[This treatment holds promise] not only for movement disorders -- Tourette's syndrome is usually associated with a lot of other comorbidities like obsessive compulsive disorder and attention-deficit symptoms -- so we do expect this to be improved with that. There is some theoretical evidence to think it might help with Parkinson's, but so far there is no data on that whatsoever, so these may be future avenues to try," he said.

  • author['full_name']

    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was funded by Abide Therapeutics.

Müller-Vahl reported relationships with Abide Therapeutics, Therapix Biosciences, and Cannafoundation. Several co-authors are employees of Abide and have received stock options in the company. Another co-author reported a relationship with Fulcrum.

Primary Source

American Academy of Neurology

Müller-Vahl K, et al "ABX-1431, A first-in-class endocannabinoid modulator, improves tics in adult patients with Tourette syndrome" AAN 2018; Abstract ES Platform 002.