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Response to elexacaftor/tezacaftor/ivacaftor in intestinal organoids derived from people with cystic fibrosis
E. Furstova, T. Dousova, J. Beranek, M. Libik, L. Fila, M. Modrak, O. Cinek, M. Macek, P. Drevinek
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't
- 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
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
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