Autism spectrum disorders (ASD) are complex neurodevelopmental diseases that affect ~1% of children in the US. Such disorders are mainly characterized by deficits in verbal communication, impaired social interaction, and limited and repetitive interests and behavior. The causes and best treatments for ASD remain uncertain. Syndromic forms of ASD, such as Rett syndrome (RTT), have a well-defined genetic basis and can be used as a prototype for idiopathic autism. The vast majority of research in ASD so far has focus on neurons. Long thought to be primarily passive support cells, recent studies have established that astrocytes, a different type of brain cell, secrete signaling molecules that powerfully stimulate the formation and function of neuronal synapses throughout the brain. Astrocytes’ dysfunctions are now known to be associated with many neurological diseases, but the exactly mechanism is unknown. The Muotri lab has identify a potential inflammatory mechanism to explain the contribution of astrocytes to ASD and the goal of this CIRM award was to screen for drugs that could act on RTT and in a subset of idiopathic ASD astrocytes to restore the proper brain homeostasis. We found 3 potential candidates that successfully act on astrocytes to reduce the inflammatory signaling. Our next steps are to validate these drug candidates in different models before starting clinical assays.