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High-Throughput Drug Discovery for a Rare Neurological Disorder: Uncovering a Novel Therapeutic Opportunity for the 19q12 Autism Spectrum Disorder [19q12 neurons baseline data]

GSE292758 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2025/03/24 Platform GPL18573
Summary
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.
Published in
High-throughput transcriptomic screening reveals entrectinib as a repositioning opportunity in 19q12 autism spectrum disorder
Guin D, Haditsch U, Bellucci JJ et al. · Scientific reports 2025 · PMID 41290998 · doi:10.1038/s41598-025-26015-y
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Direct links to NCBI, no account and no request form: the whole study as GSE292758_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 5 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1241211 and SRA study SRP572676. Searching any of these in the dataset finder brings you back here.

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