ArticleEBioMedicine2015
Measurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis.
Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- 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
- Personalized Medicine in Cystic Fibrosis: Characterization of Eight Rare CFTR Variants in Intestinal Organoids and Cellular Models.Molecular diagnosis & therapy · 2026Article
- Antisense oligonucleotide targeting the E3 ligase RFFL potentiates CFTR modulator efficacy in CF primary bronchial epithelial cells.Molecular therapy. Nucleic acids · 2025Article
- Global functional genomics reveals GRK5 as a cystic fibrosis therapeutic target synergistic with current modulators.iScience · 2025Article
- Article
- Review
- Personalized CFTR Modulator Therapy forInternational journal of molecular sciences · 2023Article
- Patient-derived cell models for personalized medicine approaches in cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2023Review
- Rescue of Rare CFTR Trafficking Mutants Highlights a Structural Location-Dependent Pattern for Correction.International journal of molecular sciences · 2023Article
- Personalized medicine: Function of CFTR variant p.Arg334Trp is rescued by currently available CFTR modulators.Frontiers in molecular biosciences · 2023Article
- Additive Potentiation of R334W-CFTR Function by Novel Small Molecules.Journal of personalized medicine · 2023Article
- Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia.Life science alliance · 2022Article
- The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway.Scientific reports · 2022Article
- Open reading frame correction using splice-switching antisense oligonucleotides for the treatment of cystic fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Gene therapy for cystic fibrosis: new tools for precision medicine.Journal of translational medicine · 2021Review
- Air-liquid interface cultures of the healthy and diseased human respiratory tract: promises, challenges and future directions.Advanced nanobiomed research · 2021Article
- Personalized Medicine Based on Nasal Epithelial Cells: Comparative Studies with Rectal Biopsies and Intestinal Organoids.Journal of personalized medicine · 2021Article
- Potential of Intestinal Current Measurement for Personalized Treatment of Patients with Cystic Fibrosis.Journal of personalized medicine · 2021Review
- Phenotyping Rare CFTR Mutations Reveal Functional Expression Defects Restored by TRIKAFTAJournal of personalized medicine · 2021Article
- Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis.Journal of experimental pharmacology · 2021Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe best investigational drug to treat cystic fibrosis (CF) patients with the most common CF-causing mutation (F508del) is VX-809 (lumacaftor) which recently succeeded in Phase III clinical trial in combination with ivacaftor. This corrector rescues F508del-CFTR from its abnormal intracellular localization to the cell surface, a traffic defect shared by all Class II CFTR mutants. Our goal here is to test the efficacy of lumacaftor in other Class II mutants in primary human bronchial epithelial (HBE) cells derived from CF patients.
methodsThe effect of lumacaftor was investigated in primary HBE cells from non-CF and CF patients with F508del/F508del, A561E/A561E, N1303K/G542X, F508del/G542X and F508del/Y1092X genotypes by measurements of Forskolin plus Genistein-inducible equivalent short-circuit current (Ieq-SC-Fsk + Gen) in perfused open-circuit Ussing chambers. Efficacy of corrector C18 was also assessed on A561E/A561E and F508del/F508del cells.
resultsOur data indicate that A561E (when present in both alleles) responds positively to lumacaftor treatment at equivalent efficacy of F508del in primary HBE cells. Similarly, lumacaftor has a positive impact on Y1092X, but not on N1303K. Our data also show that cells with only one copy of F508del-CFTR respond less to VX-809. Moreover, there is great variability in lumacaftor responses among F508del-homozygous cells from different donors. Compound C18 failed to rescue A561E-CFTR but not in F508del-CFTR, thus plausibly it has a different mechanism of action distinct from lumacaftor.
conclusionsCF patients with A561E (and likely also those with Y1029X) can potentially benefit from lumacaftor. Moreover, the methodology used here exemplifies how ex vivo approaches may apply personalized therapies to CF and possibly other respiratory diseases.
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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.