New ProteomeXchange dataset PXD059519

[ProteomeCentral Agent]

Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD059519

Summary of dataset

Status: new
Identifier: PXD059519
HostingRepository: PRIDE
Species: Homo sapiens
Title: Pluripotent stem cell-based screening uncovers sildenafil as a mitochondrial disease therapy
Submitter: David Meierhofer
LabHead: Alessandro Prigione
Description: Mitochondrial disease encompasses inherited disorders affecting mitochondrial function. A severe and untreatable form of mitochondrial disease is Leigh syndrome (LS) causing psychomotor regression and metabolic crises. To accelerate drug discovery for LS, we screen a library of 5,632 repurposable compounds in neural cells from LS patient-derived induced pluripotent stem cells (iPSCs). We identify phosphodiesterase 5 (PDE5) inhibitors as leads and prioritize sildenafil for its clinical safety. Sildenafil corrects mitochondrial membrane potential defects, restores neurodevelopmental pathways, and normalizes calcium responses in LS brain organoids. In small and large mammalian models of LS, sildenafil extends the lifespan and ameliorates disease phenotypes. Off-label individual basis treatment with sildenafil in six LS patients improves their motor function and resistance to metabolic crises. Collectively, the findings highlight the potential of iPSC-driven drug discovery a
nd position sildenafil as a promising drug candidate for mitochondrial disease.

HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD059519
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