NCE (Year 4)
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 synaptogenesis 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. We also show for the first time that iPSC-derived human neurons are able to generate synchronized neuronal networks using a multi-electrode array approach. We showed that RTT and ASD neurons behave differently from controls and defects in synchronization can be rescued with candidate drugs. Finally, we concluded our analyses on gene expression, collected from several neurons and progenitor cells derived from controls and autistic patients. We revealed and validated pathways that are altered in ASD patients, defined by specific clinical phenotypes (macrencephaly).