Evidence map›Paper›PMID 33441643›Full record

ArticleScientific reports2021

Modulation of cAMP metabolism for CFTR potentiation in human airway epithelial cells.

Jenny P Nguyen, Matthew Bianca, Ryan D Huff, Nicholas Tiessen, Mark D Inman, Jeremy A Hirota

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

6 authors at 3 institutions in 1 country.

Jenny P NguyenDivision of Respirology, Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, L8N 4A6, Canada.
Matthew BiancaDivision of Respirology, Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, L8N 4A6, Canada.
Ryan D HuffDivision of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, V6H 3Z6, Canada.
Nicholas TiessenDivision of Respirology, Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, L8N 4A6, Canada.
Mark D InmanDivision of Respirology, Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, L8N 4A6, Canada.
Jeremy A HirotaDivision of Respirology, Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, L8N 4A6, Canada. hirotaja@mcmaster.ca.
McMaster University · CAUniversity of British Columbia · CAUniversity of Waterloo · CA

Funding

CIHR
6 · The paper itself

Abstract

Cystic fibrosis (CF) is a genetic disease characterized by CF transmembrane regulator (CFTR) dysfunction. With over 2000 CFTR variants identified, in addition to known patient to patient variability, there is a need for personalized treatment. The discovery of CFTR modulators has shown efficacy in certain CF populations, however there are still CF populations without valid therapeutic options. With evidence suggesting that single drug therapeutics are insufficient for optimal management of CF disease, there has been an increased pursuit of combinatorial therapies. Our aim was to test cyclic AMP (cAMP) modulation, through ATP Binding Cassette Transporter C4 (ABCC4) and phosphodiesterase-4 (PDE-4) inhibition, as a potential add-on therapeutic to a clinically approved CFTR modulator, VX-770, as a method for increasing CFTR activity. Human airway epithelial cells (Calu-3) were used to test the efficacy of cAMP modulation by ABCC4 and PDE-4 inhibition through a series of concentration-response studies. Our results showed that cAMP modulation, in combination with VX-770, led to an increase in CFTR activity via an increase in sensitivity when compared to treatment of VX-770 alone. Our study suggests that cAMP modulation has potential to be pursued as an add-on therapy for the optimal management of CF disease.

Indexed as

AminophenolsATP-Binding Cassette, Sub-Family C ProteinsBronchiCell LineCells, CulturedCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 4Cystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDrug Therapy, CombinationEpithelial CellsHumansPhosphodiesterase 4 InhibitorsQuinolonesABCC4 protein, humanAminophenolsATP-Binding Cassette, Sub-Family C ProteinsCFTR protein, humanCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 4Cystic Fibrosis Transmembrane Conductance RegulatorivacaftorPhosphodiesterase 4 InhibitorsQuinolones

Identifiers

PMID33441643
PMCPMC7807051
OpenAlexW3118920479

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.