Evidence map›Paper›PMID 37745522›Full record

ArticlebioRxiv : the preprint server for biology2024

Cardiac glycosides restore autophagy flux in an iPSC-derived neuronal model of WDR45 deficiency.

Apostolos Papandreou, Nivedita Singh, Lorita Gianfrancesco, Dimitri Budinger, Katy Barwick, Alexander Agrotis, Christin Luft, Ying Shao, An-Sofie Lenaerts, Allison Gregory and 8 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 3 countries.

Apostolos PapandreouDevelopmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, University College London Great Ormond Street Institute of Child Health, London, UK.ORCID 0000-0001-5093-6075
Nivedita SinghLaboratory for Molecular Cell Biology, University College London, London, UK.
Lorita GianfrancescoDevelopmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, University College London Great Ormond Street Institute of Child Health, London, UK.
Dimitri BudingerDevelopmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, University College London Great Ormond Street Institute of Child Health, London, UK.
Katy BarwickDevelopmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, University College London Great Ormond Street Institute of Child Health, London, UK.
Alexander AgrotisLaboratory for Molecular Cell Biology, University College London, London, UK.
Christin LuftLaboratory for Molecular Cell Biology, University College London, London, UK.
Ying ShaoWellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK.
An-Sofie LenaertsWellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK.
Allison GregoryOregon Health and Science University, Portland, OR, USA.
Suh Young JeongOregon Health and Science University, Portland, OR, USA.
Penelope HogarthOregon Health and Science University, Portland, OR, USA.
Susan HayflickOregon Health and Science University, Portland, OR, USA.
Serena BarralDevelopmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, University College London Great Ormond Street Institute of Child Health, London, UK.ORCID 0000-0002-1430-3614
Janos Kriston-ViziLaboratory for Molecular Cell Biology, University College London, London, UK.ORCID 0000-0002-0149-145X
Paul GissenInborn Errors of Metabolism, Genetics & Genomic Medicine Programme, Great Ormond Street Institute of Child Health, University College London, London, UK.ORCID 0000-0002-9712-6122
Manju A KurianDevelopmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, University College London Great Ormond Street Institute of Child Health, London, UK.
Robin KettelerLaboratory for Molecular Cell Biology, University College London, London, UK.
MRC Laboratory for Molecular Cell Biology · GBOregon Health & Science University · USUniversity College London · GBGreat Ormond Street Hospital for Children NHS Foundation Trust · GBWellcome/MRC Cambridge Stem Cell Institute · GBGreat Ormond Street Hospital · GBMSB Medical School Berlin · DE

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
NCATS NIH HHS UL1 TR002369Wellcome Trust
6 · The paper itself

Abstract

Beta-Propeller Protein-Associated Neurodegeneration (BPAN) is one of the commonest forms of Neurodegeneration with Brain Iron Accumulation, caused by mutations in the gene encoding the autophagy-related protein, WDR45. The mechanisms linking autophagy, iron overload and neurodegeneration in BPAN are poorly understood and, as a result, there are currently no disease-modifying treatments for this progressive disorder. We have developed a patient-derived, induced pluripotent stem cell (iPSC)-based midbrain dopaminergic neuronal cell model of BPAN (3 patient, 2 age-matched controls and 2 isogenic control lines) which shows defective autophagy and aberrant gene expression in key neurodegenerative, neurodevelopmental and collagen pathways. A high content imaging-based medium-throughput blinded drug screen using the FDA-approved Prestwick library identified 5 cardiac glycosides that both corrected disease-related defective autophagosome formation and restored BPAN-specific gene expression profiles. Our findings have clear translational potential and emphasise the utility of iPSC-based modelling in elucidating disease pathophysiology and identifying targeted therapeutics for early-onset monogenic disorders.

Identifiers

PMID37745522
PMCPMC10515824
OpenAlexW4386707908

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.