ArticleJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2020
Mutation-specific dual potentiators maximize rescue of CFTR gating mutants.
Article in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Triple potentiator combinations increase the functional correction of several CFTR gating mutants.npj drug discovery · 2026Article
- Functional rescue of F508del-CFTR through revertant mutations introduced by CRISPR base editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- Rescue of Mutant CFTR Channel Activity by Investigational Co-Potentiator Therapy.Biomedicines · 2025Article
- Investigation of CFTR Function in Human Nasal Epithelial Cells Informs Personalized Medicine.American journal of respiratory cell and molecular biology · 2024Article
- Organic Synthesis and Current Understanding of the Mechanisms of CFTR Modulator Drugs Ivacaftor, Tezacaftor, and Elexacaftor.Molecules (Basel, Switzerland) · 2024Review
- Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.The Journal of physiology · 2024Article
- Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations.Frontiers in pharmacology · 2024Article
- Additive Potentiation of R334W-CFTR Function by Novel Small Molecules.Journal of personalized medicine · 2023Article
- Personalized medicine: Function of CFTR variant p.Arg334Trp is rescued by currently available CFTR modulators.Frontiers in molecular biosciences · 2023Article
- Molecular mechanisms of cystic fibrosis - how mutations lead to misfunction and guide therapy.Bioscience reports · 2022Review
- Molecular Dynamics and Theratyping in Airway and Gut Organoids Reveal R352Q-CFTR Conductance Defect.American journal of respiratory cell and molecular biology · 2022Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- A small molecule CFTR potentiator restores ATP-dependent channel gating to the cystic fibrosis mutant G551D-CFTR.British journal of pharmacology · 2022Article
- Molecular dynamics and functional characterization of I37R-CFTR lasso mutation provide insights into channel gating activity.iScience · 2022Article
- Elexacaftor co-potentiates the activity of F508del and gating mutants of CFTR.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2021Article
- A Precision Medicine Approach to Optimize Modulator Therapy for Rare CFTR Folding Mutants.Journal of personalized medicine · 2021Article
- New Therapies to Correct the Cystic Fibrosis Basic Defect.International journal of molecular sciences · 2021Review
- Article
- Alteration of Membrane Cholesterol Content Plays a Key Role in Regulation of Cystic Fibrosis Transmembrane Conductance Regulator Channel Activity.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe potentiator ivacaftor (VX-770) has been approved for therapy of 38 cystic fibrosis (CF) mutations (∼10% of the patient population) associated with a gating defect of the CF transmembrane conductance regulator (CFTR). Despite the success of VX-770 treatment of patients carrying at least one allele of the most common gating mutation G551D-CFTR, some lung function decline and P. aeruginosa colonization persist. This study aims at identifying potentiator combinations that can considerably enhance the limited channel activity of a panel of CFTR gating mutants over monotherapy.
methodsThe functional response of 13 CFTR mutants to single potentiators or systematic potentiator combinations was determined in the human bronchial epithelial cell line CFBE41o- and a subset of them was confirmed in primary human nasal epithelia (HNE).
resultsIn six out of thirteen CFTR missense mutants the fractional plasma membrane (PM) activity, a surrogate measure of CFTR channel gating, reached only ∼10-50% of WT channel activity upon VX-770 treatment, indicating incomplete gating correction. Combinatorial potentiator profiling and cluster analysis of mutant responses to 24 diverse investigational potentiators identified several compound pairs that improved the gating activity of R352Q-, S549R-, S549N-, G551D-, and G1244E-CFTR to ∼70-120% of the WT. Similarly, the potentiator combinations were able to confer WT-like function to G551D-CFTR in patient-derived human nasal epithelia.
conclusionThis study suggests that half of CF patients with missense mutations approved for VX-770 administration, could benefit from the development of dual potentiator 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.