Abstract
Autism spectrum disorder (ASD) is characterised by the concomitant occurrence of impaired social interaction; restricted, perseverative and stereotypical behaviour; and abnormal communication skills. Recent epidemiological studies have reported a dramatic increase in the prevalence of ASD with as many as 1 in every 59 children being diagnosed with ASD. The fact that ASD appears to be principally genetically driven, and may be reversible postnatally, has raised the exciting possibility of using gene therapy as a disease-modifying treatment. Such therapies have already started to seriously impact on human disease and particularly monogenic disorders (e.g. metachromatic leukodystrophy, SMA type 1). In regard to ASD, technical advances in both our capacity to model the disorder in animals and also our ability to deliver genes to the central nervous system (CNS) have led to the first preclinical studies in monogenic ASD, involving both gene replacement and silencing. Furthermore, our increasing awareness and understanding of common dysregulated pathways in ASD have broadened gene therapy's potential scope to include various polygenic ASDs. As this review highlights, despite a number of outstanding challenges, gene therapy has excellent potential to address cognitive dysfunction in ASD.