The future of autism medicine: analyzing drugs in development

Autism spectrum disorder (ASD) is a complex disease characterized by difficulties in social interaction and the presence of restricted and repetitive behaviors. It was identified over 80 years ago with ~ 2.8% of children in the United States being affected. Many factors, including genetic and environmental, contribute to the development of the disease. Hundreds of genes have been identified as being associated with ASD. However, there is no FDA-approved pharmacological treatment specifically addressing its core symptoms, although the FDA has approved two drugs to treat irritability and aggression in ASD patients. Non-pharmacological treatments, particularly behavioral therapies, remain the primary approach for symptom management. Nevertheless, many drugs targeting ASD-associated genes are in development. In this work, the pharmacological treatments that have entered clinical trials were identified and grouped based on clinical stage, drug modality, and drug target. The results showed that most drugs in clinical development are small molecules, with a focus on improving synapse function. Certain drugs, including bumetanide, L1-79, and cannabidiol, have demonstrated significant improvements in treating ASD core symptoms based on available clinical data. Additionally, expression profiles of the drug-targeted genes were evaluated. Several of these genes were found to be differentially expressed in ASD patients, providing a stronger rationale for therapeutic targeting. Clinical activity congregated around drugs targeting moderately differentially expressed genes, presumably because targeting lower gene expression was bereft of efficacy, while targeting high differential gene expression could reasonably be inferred to cause toxicity and off-target effects.