Arbaclofen in Children and Adolescents With ASD

Autism Spectrum Disorder (ASD) is a clinically and etiologically heterogeneous neurodevelopmental condition affecting approximately 1% of the population. The core symptoms of ASD are deficits in social communication and the presence of repetitive and restricted behaviours and interests, including sensory anomalies. Currently, there are no effective medical treatments for the core symptoms of ASD, and families frequently use costly non evidence based interventions. Developing drugs for ASD has been challenging because of a limited understanding of its underlying pathophysiology(ies), and difficulties modelling it in vitro and in vivo. A recent study from EU‐AIMS reported, for the first time in ASD, that differences in E‐I balance can be 'shifted' using a GABA acting drug (riluzole), and that abnormalities in functional connectivity can be 'normalised' by targeting E‐I, even in adults. This offers promise that drugs targeting specific parts of the GABA pathway may improve symptoms. The aim of the investigator's project is to conduct a double‐blind Randomized Control Trial (RCT) focused on GABA/glutamate equilibrium, to assess the efficacy of a drug that targets core and/or comorbid symptoms in ASD. Arbaclofen is a selective GABA‐B receptor agonist and augments GABA‐ergic activity, inhibits presynaptic release of glutamate, inhibits postsynaptic transmission, and modulates intracellular signalling. Through elevation of GABA‐ergic inhibitory activity, Arbaclofen may act to alleviate ASD symptoms with social anxiety and emotional hyperarousal. Hypothesis: Arbaclofen will be superior to placebo in improving social function as measured by the Vineland‐3 social domain.