High-Throughput Drug Discovery for a Rare Neurological Disorder: Uncovering a Novel Therapeutic Opportunity for the 19q12 Autism Spectrum Disorder [19q12 neurons baseline data]
Discovering new and viable therapies for genetic diseases is a time consuming and cost intensive process. This is even more challenging for rare disorders that affect a small fraction of the population and do not incentivise research and development in the traditional drug discovery lifecycle. There is therefore a need for scalable and efficient solutions for discovering novel therapies for these rare disorders. In this study, we highlight how a high-throughput drug discovery engine was utilized to uncover drugs at scale that normalized the signature for a rare neurological neurodevelopmental disease, 19q12 autism spectrum disorder associated with deficiencies in ZNF536 and TSHZ3. We do this by uncovering and understanding the full 360o view of the biological impact of the drug in a relevant cell line via transcriptomics. This platform, in combination with a statistically viable n-of-1 trial, was able to quickly uncover and utilize a novel therapeutic potential of a previously approved drug for a patient living with from 19q12 autism spectrum disorder. Overall design: RNA-seq profiling of a 19q12 patient iPSC-derived neurons at 5 timepoints during neuronal differentiation, wildtype neurons treated with Entrectinib at 10 concentrations and whole blood of patient pre- and post-treatment with Entrectinib.