Response to elexacaftor/tezacaftor/ivacaftor in intestinal organoids derived from people with cystic fibrosis
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
34348870
DOI
10.1016/j.jcf.2021.07.006
PII: S1569-1993(21)01304-7
Knihovny.cz E-resources
- Keywords
- CFTR sequence, Cystic fibrosis, Elexacaftor, Intestinal organoids, Ivacaftor, Tezacaftor,
- MeSH
- Chloride Channel Agonists pharmacology therapeutic use MeSH
- Aminophenols pharmacology therapeutic use MeSH
- Benzodioxoles pharmacology therapeutic use MeSH
- Quinolones MeSH
- Cystic Fibrosis * drug therapy genetics MeSH
- Drug Combinations MeSH
- Indoles MeSH
- Humans MeSH
- Mutation MeSH
- Organoids * MeSH
- Cystic Fibrosis Transmembrane Conductance Regulator genetics MeSH
- Pyrazoles MeSH
- Pyridines MeSH
- Pyrrolidines MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Chloride Channel Agonists MeSH
- Aminophenols MeSH
- Benzodioxoles MeSH
- Quinolones MeSH
- elexacaftor MeSH Browser
- Drug Combinations MeSH
- Indoles MeSH
- ivacaftor MeSH Browser
- Cystic Fibrosis Transmembrane Conductance Regulator MeSH
- Pyrazoles MeSH
- Pyridines MeSH
- Pyrrolidines MeSH
- tezacaftor MeSH Browser
Superior efficacy of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) over tezacaftor/ivacaftor (TEZ/IVA) in people with cystic fibrosis (CF) and Phe508del/Phe508del genotype was shown in clinical trials. We utilized intestinal organoid approach to compare in vitro responses to these 2 CFTR modulator drug combinations and to check potential inter-individual variability in therapeutic response to the triple combination. Organoids from 17 subjects with Phe508del/Phe508del were screened with forskolin induced swelling assay. Significantly larger swelling, when exposed to ELX/TEZ/IVA as compared to TEZ/IVA, was observed in 16 of them. However, 1 sample showed no additional effect of ELX. The finding of unique CFTR variants in this sample indicates that genetic traits other than CF-causing CFTR mutation are worth exploring as they may have an impact on the definitive modulator drug response.
References provided by Crossref.org
