Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
Abide Therapeutics, San Diego, CA, USA.
Pharmacopsychiatry. 2022 May;55(3):148-156. doi: 10.1055/a-1675-3494. Epub 2021 Nov 30.
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.
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.
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.
In this exploratory trial, a single dose of Lu AG06466 showed statistically significant positive effects on key measures of TS symptoms.
妥瑞氏症（TS）是一种复杂的神经发育障碍，其特征是慢性运动和发声抽动。虽然缺乏始终有效的治疗方法，但有证据表明，内源性大麻素系统的调节可能是有益的。Lu AG06466（以前称为 ABX-1431）是一种高度选择性的单酰基甘油脂肪酶抑制剂，是负责降解内源性大麻素配体 2-花生四烯酸甘油的主要酶。这项探索性研究旨在确定 Lu AG06466 与安慰剂相比对 TS 患者抽动和其他症状的影响。
在这项 1b 期交叉研究中，20 名正在接受标准治疗药物治疗的 TS 成年患者被随机分为 Lu AG06466（40mg）或安慰剂的单剂量禁食组，在第 1 期后进入第 2 期。使用各种量表在治疗前后的不同时间点评估对抽动、预感冲动和精神共病的影响。
所有量表均显示出抽动总体减少的趋势，其中三种抽动量表中的两种（包括耶鲁全球抽动严重程度量表的总抽动评分）在不同时间点显示 Lu AG06466 与安慰剂相比具有显著的治疗效果。与安慰剂相比，Lu AG06466 治疗可显著减少预感冲动。Lu AG06466 的单剂量通常耐受性良好，最常见的不良事件是头痛、嗜睡和疲劳。
在这项探索性试验中，Lu AG06466 的单剂量显示对 TS 症状的关键测量指标具有统计学上显著的积极影响。
