Evidence map›Paper›PMID 36293514›Full record

ArticleInternational journal of molecular sciences2022

Drug Repurposing for Cystic Fibrosis: Identification of Drugs That Induce CFTR-Independent Fluid Secretion in Nasal Organoids.

Lisa W Rodenburg, Livia Delpiano, Violeta Railean, Raquel Centeio, Madalena C Pinto, Shannon M A Smits, Isabelle S van der Windt, Casper F J van Hugten, Sam F B van Beuningen, Remco N P Rodenburg and 6 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.3field-weighted citation impact, top 10% of its field
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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Lung organoids: a new frontier in neonatology and paediatric respiratory medicine.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  7. Article
  8. Dynamic regulation of airway surface liquid pH by TMEM16A and SLC26A4 in cystic fibrosis nasal epithelia with rare mutations.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Article
  10. Article
  11. Open questions in human lung organoid research.Frontiers in pharmacology · 2022
    Review
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

16 authors at 4 institutions in 4 countries.

Lisa W RodenburgDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.ORCID 0000-0002-8113-4304
Livia DelpianoBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.ORCID 0000-0002-2319-4456
Violeta RaileanBioISI-Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisboa, Portugal.
Raquel CenteioPhysiological Institute, University of Regensburg, D-93053 Regensburg, Germany.
Madalena C PintoBioISI-Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisboa, Portugal.ORCID 0000-0001-9045-269X
Shannon M A SmitsDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.
Isabelle S van der WindtDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.
Casper F J van HugtenDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.
Sam F B van BeuningenDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.ORCID 0000-0001-6166-196X
Remco N P RodenburgDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.ORCID 0000-0002-0149-8731
Cornelis K van der EntDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.
Margarida D AmaralBioISI-Biosystems and Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisboa, Portugal.ORCID 0000-0002-0828-8630
Karl KunzelmannPhysiological Institute, University of Regensburg, D-93053 Regensburg, Germany.
Michael A GrayBiosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Jeffrey M BeekmanDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.
Gimano D AmatngalimDepartment of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Member of ERN-LUNG, 3584 EA Utrecht, The Netherlands.ORCID 0000-0003-3442-1754
Utrecht University · NLUniversity of Lisbon · PTNewcastle University · GBUniversity of Regensburg · DE

Funding

Cystic Fibrosis Trust SRC013Fundação para a Ciência e Tecnologia UIDB/04046/2020Fundação para a Ciência e Tecnologia UIDP/04046/2020
6 · The paper itself

Abstract

Individuals with cystic fibrosis (CF) suffer from severe respiratory disease due to a genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which impairs airway epithelial ion and fluid secretion. New CFTR modulators that restore mutant CFTR function have been recently approved for a large group of people with CF (pwCF), but ~19% of pwCF cannot benefit from CFTR modulators Restoration of epithelial fluid secretion through non-CFTR pathways might be an effective treatment for all pwCF. Here, we developed a medium-throughput 384-well screening assay using nasal CF airway epithelial organoids, with the aim to repurpose FDA-approved drugs as modulators of non-CFTR-dependent epithelial fluid secretion. From a ~1400 FDA-approved drug library, we identified and validated 12 FDA-approved drugs that induced CFTR-independent fluid secretion. Among the hits were several cAMP-mediating drugs, including β2-adrenergic agonists. The hits displayed no effects on chloride conductance measured in the Ussing chamber, and fluid secretion was not affected by TMEM16A, as demonstrated by knockout (KO) experiments in primary nasal epithelial cells. Altogether, our results demonstrate the use of primary nasal airway cells for medium-scale drug screening, target validation with a highly efficient protocol for generating CRISPR-Cas9 KO cells and identification of compounds which induce fluid secretion in a CFTR- and TMEM16A-indepent manner.

Indexed as

Cystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorAdrenergic AgonistsChloridesDrug RepositioningEpithelial CellsHumansOrganoidsAdrenergic AgonistsCFTR protein, humanChloridesCystic Fibrosis Transmembrane Conductance Regulatorcystic fibrosisdrug repurposingnasal organoidsscreening assayTMEM16A

Identifiers

PMID36293514
PMCPMC9603984
OpenAlexW4307160324

What OpenQuestion holds

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LicenceCC BY
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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.