ArticleThorax2005
Sildenafil (Viagra) corrects DeltaF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis.
Article in Thorax, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 33 papers, 1 of them a synthesis that pooled 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.
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.
Does a Nasal Instillation of Vardenafil Normalize the Nasal Potential Difference in Cystic Fibrosis Patients Homozygous for the F508del Mutation? A Randomized, Double Blind, Placebo-controlled Study.
Phase II Study of the Effects of Sildenafil on CFTR-dependent Ion Transport Activity
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023Pooled it
- Pharmacokinetics and tolerability of oral sildenafil in adults with cystic fibrosis lung disease.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2015Trial
- Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies.Advances in respiratory medicine · 2024Review
- Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Pathological Significance of Macrophages in Erectile Dysfunction Including Peyronie's Disease.Biomedicines · 2021Review
- Riociguat: Clinical research and evolving role in therapy.British journal of clinical pharmacology · 2021Review
- The significance of a lack of rhinorrhea in severe coronavirus 19 lung disease.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Article
- Review
- Sildenafil improves exercise capacity in patients with cystic fibrosis: a proof-of-concept clinical trial.Therapeutic advances in chronic disease · 2019Article
- Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives.Clinical pharmacology : advances and applications · 2016Review
- Changing the Paradigm - Treating the Basic Defect in Cystic Fibrosis.Indian journal of pediatrics · 2015Review
- Roscovitine is a proteostasis regulator that corrects the trafficking defect of F508del-CFTR by a CDK-independent mechanism.British journal of pharmacology · 2014Article
- Correction of defective CFTR/ENaC function and tightness of cystic fibrosis airway epithelium by amniotic mesenchymal stromal (stem) cells.Journal of cellular and molecular medicine · 2014Article
- Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain.EMBO molecular medicine · 2013Article
- Article
- Ouabain Mimics Low Temperature Rescue of F508del-CFTR in Cystic Fibrosis Epithelial Cells.Frontiers in pharmacology · 2012Article
- PDE5 Inhibitors as Potential Tools in the Treatment of Cystic Fibrosis.Frontiers in pharmacology · 2012Article
- The challenge of exploiting ABCG2 in the clinic.Current pharmaceutical biotechnology · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost patients with cystic fibrosis (CF) have a DeltaF508 mutation resulting in abnormal retention of mutant gene protein (DeltaF508-CFTR) within the cell. This study was undertaken to investigate DeltaF508-CFTR trafficking in native cells from patients with CF with the aim of discovering pharmacological agents that can move DeltaF508-CFTR to its correct location in the apical cell membrane.
methodNasal epithelial cells were obtained by brushing from individuals with CF. CFTR location was determined using immunofluorescence and confocal imaging in untreated cells and cells treated with sildenafil. The effect of sildenafil treatment on CFTR chloride transport function was measured in CF15 cells using an iodide efflux assay.
resultsIn most untreated CF cells DeltaF508-CFTR was mislocalised within the cell at a site close to the nucleus. Exposure of cells to sildenafil (2 hours at 37 degrees C) resulted in recruitment of DeltaF508-CFTR to the apical membrane and the appearance of chloride transport activity. Sildenafil also increased DeltaF508-CFTR trafficking in cells from individuals with CF with a single copy DeltaF508 (DeltaF508/4016ins) or with a newly described CF trafficking mutation (R1283M).
conclusionsThe findings provide proof of principle for sildenafil as a DeltaF508-CFTR trafficking drug and give encouragement for future testing of sildenafil and related PDE5 inhibitors in patients with CF.
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What OpenQuestion holds
Registered trials
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.