Authors: Dorit Trudler, Swagata Ghatak, Michael Bula, James Parker, Maria Talantova, Melissa Luevanos, Sergio Labra, Titas Grabauskas, Sarah Moore Noveral, Mayu Teranaka, Emily Schahrer, Nima Dolatabadi, Clare Bakker, Kevin Lopez, Abdullah Sultan, Parth Patel, Agnes Chan, Yongwook Choi, Riki Kawaguchi, Pawel Stankiewicz, Ivan Garcia-Bassets, Piotr Kozbial, Michael G. Rosenfeld, Nobuki Nakanishi, Daniel H. Geschwind, Shing Fai Chan, Wei Lin, Nicholas J. Schork, Rajesh Ambasudhan and Stuart A. Lipton
Molecular Psychiatry, 30 September 2024
Researchers use cerebral organoids on Axion’s Maestro MEA system to explore the pathogenesis of MEF2C haploinsufficiency syndrome (MHS) and assess the impact of NitroSynapsin treatment.
MEF2C haploinsufficiency syndrome (MHS), a rare and severe form of autism spectrum disorder (ASD), has not been investigated thoroughly in human models. In this study, researchers used MHS patient hiPSC-derived neurons and organoids to model MHS and study the pathogenic mechanisms. To evaluate the activity of patient hiPSC-derived neural cultures and cerebral organoids in real time in vitro, the team used Axion BioSystems’ noninvasive Maestro microelectrode array (MEA) platform, finding that MHS neurons and organoids exhibited a hyperactive and hypersynchronous phenotype suggestive of ASD. Importantly, this phenotype was rescued by treatment with NitroSynapsin, an experimental compound that blocks excessive excitatory synaptic activity. Furthermore, MEFC2 is involved in regulation of other ASD-associated genes. Given that excessive glutamate may contribute to these other ASD phenotypes, a similar approach may hold promise for other forms of ASD as well.
