Novel treatments for autism spectrum disorder based on genomics and systems biology

Background: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with a complex underlying genetic architecture. There are currently no known pharmacologic treatments for the core ASD symptoms of social deficits and restricted/ repetitive behavior. However, there are dozens of clinical trials currently underway that are testing the impact of novel and existing agents on core and associated symptoms in ASD. Methods: We present a narrative synthesis of the historical and contemporary challenges to drug discovery in ASD. We then provide an overview of novel treatments currently under investigation from a genomics and systems biology perspective. Results: Data driven network and cluster analyses suggest alterations in transcriptional regulation, chromatin remodelling, synaptic transmission, neuropeptide signalling, and/or immunologicalmechanismsmay contribute to or underlie the development of ASD. Agents and upcoming trials targeting each of the above listed systems are reviewed. Conclusion: Identifying effective pharmacologic treatments for the core and associated symptomdomains in ASD will require further collaboration and innovation in the areas of outcomemeasurement, biomarker research, and genomics, as well as systematic efforts to identify and treat subgroups of individuals with ASD who may be differentially responsive to specific treatments. (C) 2021 Published by Elsevier Inc.

Automated summary

Autism spectrum disorder is a neurodevelopmental disorder with no known pharmacologic treatments for core symptoms. However, numerous clinical trials are investigating novel and existing agents for their impact on symptoms. Alterations in transcriptional regulation, chromatin remodeling, synaptic transmission, neuropeptide signaling, and immunological mechanisms may contribute to the development of ASD. Further collaboration and innovation in outcome measurement, biomarker research, genomics, and subgroup identification are necessary for identifying effective pharmacologic treatments.