Year 3

The goal of this CIRM translational award is to generate a hiPSC-based drug-screening platform to identify potential therapies or biomarkers for ASDs. We have made significant progress toward this goal by working on validating several neuronal phenotypes derived from iPSC from Rett syndrome (RTT) and idiopathic autistic patients. We also made significant progress to optimize the readout for our screening platform. This was important to speed up drug discovery. Using RTT iPSC as a prototype, we showed that we could rescue defect in synaptogenesis using a collection of FDA-approved drugs. Finally, we initiate our analyses on gene expression, collected from several neurons and progenitor cells derived from controls and autistic patients. We expect to find pathways that are altered in subgroups of patients, defined by specific clinical phenotypes. Here, we describe the results of our drug screening, using FDA-approved drugs in a repurposing strategy. We also show for the first time that iPSC-derived human neurons are able to generate synchronized neuronal networks. RTT neurons behave differently from controls. Our focus now is on the completion of our gene expression analyses and to validate positive drugs using a battery of secondary cellular assays.