Grant: Project Grant

Fragile-X syndrome (FXS) is the primary hereditary cause of intellectual disability and the first monogenic cause of autism spectrum disorder. There is currently no cure for FXS, and the few therapeutic options available focus solely on the management of behavioural and cognitive symptoms, with limited efficacy. Recent advances now allows investigating interventions that target the mechanisms causally involved in the disorder, and potentially modify its natural course. In that regard, the endocannabinoid system (eCB) emerges as a particularly appealing therapeutic target for FXS. The overarching goal of the proposed project is to measure the eCB system in FXS, and assess the behavioural and neurophysiological effects of cannabidiol (CBD) in patients with FXS. The project is divided into three main aims: 1) To measure the abnormalities affecting the eCB in humans with FXS; 2) To quantify the effects of CBD administration on the main neurotransmitter systems in the brain of FXS patients; and 3) To establish the effects of CBD on behavioural, emotional, and cognitive difficulties of patients with FXS. Design: To achieve these aims, 60 participants with FXS will take part in a cross-over study for a total duration of 36 weeks. Sixty (60) healthy controls will also take part in the study to provide reference ranges. Techniques: (Aim 1) the eCB system will be measured using biochemical analyses performed on blood samples; (Aim 2) neurotransmitter concentration levels and their functional impacts will be assessed with neuroimaging tools, namely magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS). (Aim 3) The efficacy of CBD on behaviour, emotion, and cognition of patients with FXS will be measured with well-validated questionnaires and psychometric tests. Results from this study will provide important information regarding the mechanisms of action of CBD and its efficacy as a treatment for FXS.