ArticleScience translational medicine2014
Potentiator ivacaftor abrogates pharmacological correction of ΔF508 CFTR in cystic fibrosis.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
203 citing papers in PubMed, 305 citations in OpenAlex.
- Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2025Trial
- Sweat rate analysis of ivacaftor potentiation of CFTR in non-CF adults.Scientific reports · 2018Trial
- In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies.Pediatric pulmonology · 2017Trial
- A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.Cell death and differentiation · 2016Trial
- Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR.The New England journal of medicine · 2015Trial
- Triple potentiator combinations increase the functional correction of several CFTR gating mutants.npj drug discovery · 2026Article
- Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis.Cell stem cell · 2026Article
- Chronic and acute modulator treatment restore wild-type-like activity and stability to the primary cystic fibrosis-causingProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Barriers to the Pharmacologic Rescue of W1282X CFTR.Biochemistry · 2026Article
- Greenness, Whiteness, and Blueness Assessment With a Novel and Fully Validated HPLC Method for Simultaneous Analysis of Lumacaftor and Ivacaftor in Sweat.International journal of analytical chemistry · 2026Article
- Reflection confocal microscopy for quantitative assessment of airway surface layer dysregulation and pharmacological rescue in cystic fibrosis under near-physiological conditions.Scientific reports · 2025Article
- Chronic pancreatitis patient-derived organoids reveal new paths to precision therapeutics.bioRxiv : the preprint server for biology · 2025Article
- Article
- TGF-β induces excessive pulmonary IL-6 secretion in cystic fibrosis via PI3K.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Lumacaftor inhibits channel activity of rescued F508del cystic fibrosis transmembrane conductance regulator.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- The potentiator ivacaftor is essential for pharmacological restoration of F508del-CFTR function and mucociliary clearance in cystic fibrosis.JCI insight · 2025Article
- Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators.iScience · 2025Article
- Inflammatory response in CF airway epithelial cells: a comparative study of modulators and wild-type CFTR rescue.Frontiers in pharmacology · 2025Article
- BOS-318 treatment enhances elexacaftor-tezacaftor-ivacaftor-mediated improvements in airway hydration and mucociliary transport.ERJ open research · 2025Article
- Neutrophil extracellular traps and interleukin-1β in cystic fibrosis lung disease.Frontiers in immunology · 2025Review
143 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR). Newly developed "correctors" such as lumacaftor (VX-809) that improve CFTR maturation and trafficking and "potentiators" such as ivacaftor (VX-770) that enhance channel activity may provide important advances in CF therapy. Although VX-770 has demonstrated substantial clinical efficacy in the small subset of patients with a mutation (G551D) that affects only channel activity, a single compound is not sufficient to treat patients with the more common CFTR mutation, ΔF508. Thus, patients with ΔF508 will likely require treatment with both correctors and potentiators to achieve clinical benefit. However, whereas the effectiveness of acute treatment with this drug combination has been demonstrated in vitro, the impact of chronic therapy has not been established. In studies of human primary airway epithelial cells, we found that both acute and chronic treatment with VX-770 improved CFTR function in cells with the G551D mutation, consistent with clinical studies. In contrast, chronic VX-770 administration caused a dose-dependent reversal of VX-809-mediated CFTR correction in ΔF508 homozygous cultures. This result reflected the destabilization of corrected ΔF508 CFTR by VX-770, markedly increasing its turnover rate. Chronic VX-770 treatment also reduced mature wild-type CFTR levels and function. These findings demonstrate that chronic treatment with CFTR potentiators and correctors may have unexpected effects that cannot be predicted from short-term studies. Combining these drugs to maximize rescue of ΔF508 CFTR may require changes in dosing and/or development of new potentiator compounds that do not interfere with CFTR stability.
Indexed as
Identifiers
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.