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Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids

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By Carmen Menacho, Satoshi Okawa, Iris Alvarez-Merz, Annika Wittich, Mikel Muñoz-Oreja, Pawel Lisowski, Mario Martin, Mario Martín, Tancredi Massimo Pentimalli, Shiri Zakin, Mathuravani A. Thevandavakkam, Caleb Jerred, Selene Lickfett, Laura Petersilie, Agnieszka Rybak-Wolf, Diran Herebian, Gizem Inak, Susanne Brodesser, Andrea Zaliani, Barbara Mlody, Justin A. Donnelly, Kasey Woleben, Francesc Xavier Soriano, Jose C Fernandez-Checa, Natascia Ventura, Sidney Cambridge, Ertan Mayatepek, Markus Schuelke, Nikolaus Rajewsky, Andrea Rossi, Alex Peralvarez-Marin, Felix Distelmaier, Ethan Perlstein, Ian Holt, Emma Puighermanal, Ole Pless, Christine Rose, Antonio del Sol, Alessandro Prigione, Annette Seibt, Antonella Spinazzola
| Nature Verified
Abstract Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, we here develop a deep learning algorithm tailored for cell type-specific drug repurposing screening.
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