ArticleJCI insight2018
Residual function of cystic fibrosis mutants predicts response to small molecule CFTR modulators.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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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.
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Who cites it
61 citing papers in PubMed.
- Elexacaftor-tezacaftor-ivacaftor for individuals with residual CFTR activity: an open-label, nonrandomized clinical trial.Annals of the American Thoracic Society · 2026Article
- Profiling the CFTR Variant Selectivity and Off-Target Interactions of VX-121.bioRxiv : the preprint server for biology · 2026Article
- Cigarette Smoke Induces Canonical Stress Granule Formation in Human Bronchial Epithelial Cells in Reactive Oxygen Species- and PERK-Dependent Manners.Biomolecules · 2026Article
- Barriers to the Pharmacologic Rescue of W1282X CFTR.Biochemistry · 2026Article
- Identity, functional consequences, and context effects of amino acids inserted during suppression of CFTR nonsense mutations.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026Article
- A novel drug series optimized to address cystic fibrosis and other CFTR deficiency diseases of human airways.npj drug discovery · 2025Article
- Molecular and pharmacological evaluation of rare, cystic fibrosis-causing missense mutations of the CFTR channel.The Journal of physiology · 2025Article
- VX-770, CInternational journal of molecular sciences · 2025Article
- Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases.Israel journal of chemistry · 2024Article
- Investigation of CFTR Function in Human Nasal Epithelial Cells Informs Personalized Medicine.American journal of respiratory cell and molecular biology · 2024Article
- Article
- tRNA therapeutics for genetic diseases.Nature reviews. Drug discovery · 2024Review
- Mg2+ supplementation treats secretory diarrhea in mice by activating calcium-sensing receptor in intestinal epithelial cells.The Journal of clinical investigation · 2024Article
- Ligand-based virtual-screening identified a novel CFTR ligand which improves the defective cell surface expression of misfolded ABC transporters.Frontiers in pharmacology · 2024Article
- Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.The Journal of physiology · 2024Article
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
- Article
- A Novel 7ACS medicinal chemistry letters · 2023Article
- General trends in the effects of VX-661 and VX-445 on the plasma membrane expression of clinical CFTR variants.Cell chemical biology · 2023Article
- Article
1 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
14 authors.
Funding
Abstract
Treatment of individuals with cystic fibrosis (CF) has been transformed by small molecule therapies that target select pathogenic variants in the CF transmembrane conductance regulator (CFTR). To expand treatment eligibility, we stably expressed 43 rare missense CFTR variants associated with moderate CF from a single site in the genome of human CF bronchial epithelial (CFBE41o-) cells. The magnitude of drug response was highly correlated with residual CFTR function for the potentiator ivacaftor, the corrector lumacaftor, and ivacaftor-lumacaftor combination therapy. Response of a second set of 16 variants expressed stably in Fischer rat thyroid (FRT) cells showed nearly identical correlations. Subsets of variants were identified that demonstrated statistically significantly higher responses to specific treatments. Furthermore, nearly all variants studied in CFBE cells (40 of 43) and FRT cells (13 of 16) demonstrated greater response to ivacaftor-lumacaftor combination therapy than either modulator alone. Together, these variants represent 87% of individuals in the CFTR2 database with at least 1 missense variant. Thus, our results indicate that most individuals with CF carrying missense variants are (a) likely to respond modestly to currently available modulator therapy, while a small fraction will have pronounced responses, and (b) likely to derive the greatest benefit from combination therapy.
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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.