A Human Stem Cell-Based Model to Study Autism-Linked Endoplasmic Reticulum Stress and Initial Testing of Therapeutic StrategiesShort Title
Child Health Institute of New Jersey, Rutgers University
Autism has been linked to mutations in some of the genes that encode for neuronal proteins that enable them to make synaptic connections. In the last decade several genetic abnormalities in two extensively replicated genes, NLGN3 and CNTNAP2, have been reported.
We recently discovered that specific autism related mutations affect the amount of protein that is able to reach the synaptic connections and cause biochemical stress to the neurons, providing evidence for a novel mechanism of autism etiology. Although human neurons from autistic patients are not directly accessible, we now have a technology that can convert patient skin biopsy or blood cells into functional neurons. Given the identification of mutations in the aforementioned genes in individuals with autism, this project is aimed at characterizing the pathogenic role of these mutations in a novel but controlled system to generate human neurons to model the â€œdisease in a dishâ€ and screen novel potential therapeutic agents. We also have the opportunity to test these potential therapeutic agents with neurons generated from selected samples collected from New Jersey residents with autism. The findings will help develop novel biomarkers for effective screening in a larger pool of individuals with autism.