A drug-screening platform for autism spectrum disorders using human neurons and astrocytes

National Center For Advancing Translational Sciences

Investigators

Abstract

This project aims to utilize high throughput screening to rescue ASD-derived astrocytic phenotypes in 3D neuron-astrocyte co-cultures. During this period, the collaborative team utilized the previously optimized high-throughput screening assay to screen a focused library, and a number of candidate compounds were identified that reduced toxic IL-6/8 levels. These candidates were advanced for testing in brain organoids and in vivo experiments using heterozygous Setd5 knockout mice, subjected to a battery of autism-related behavioral tests, to observe if they can rescue the disease phenotype. The mechanisms of action of these hits are currently being validated, and their activity profiles are being characterized in follow-up assays, such as glutamate uptake and synapse formation, using neuron-astrocyte co-cultures and testing in brain organoids in dose response.