PXD059519-1

PXD059519 is an original dataset announced via ProteomeXchange.

Title	Pluripotent stem cell-based screening uncovers sildenafil as a mitochondrial disease therapy
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 and position sildenafil as a promising drug candidate for mitochondrial disease.
HostingRepository	PRIDE
AnnounceDate	2026-02-10
AnnouncementXML	Submission_2026-02-09_21:43:23.459.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-07 12:25:15	ID requested
⏵ 1	2026-02-09 21:43:23	announced

Dataset with its publication pending

submitter keyword: None

Alessandro Prigione
contact affiliation	Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich Heine University, Duesseldorf, Germany
contact email	alessandro.prigione@hhu.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/02/PXD059519

PRIDE project URI

• PRIDE
  1. PXD059519
     1. Label: PRIDE project
     2. Name: Pluripotent stem cell-based screening uncovers sildenafil as a mitochondrial disease therapy