Response to elexacaftor/tezacaftor/ivacaftor in intestinal organoids derived from people with cystic fibrosis
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
34348870
DOI
10.1016/j.jcf.2021.07.006
PII: S1569-1993(21)01304-7
Knihovny.cz E-zdroje
- Klíčová slova
- CFTR sequence, Cystic fibrosis, Elexacaftor, Intestinal organoids, Ivacaftor, Tezacaftor,
- MeSH
- aktivátory chloridových kanálů farmakologie terapeutické užití MeSH
- aminofenoly farmakologie terapeutické užití MeSH
- benzodioxoly farmakologie terapeutické užití MeSH
- chinolony MeSH
- cystická fibróza * farmakoterapie genetika MeSH
- fixní kombinace léků MeSH
- indoly MeSH
- lidé MeSH
- mutace MeSH
- organoidy * MeSH
- protein CFTR genetika MeSH
- pyrazoly MeSH
- pyridiny MeSH
- pyrrolidiny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aktivátory chloridových kanálů MeSH
- aminofenoly MeSH
- benzodioxoly MeSH
- chinolony MeSH
- elexacaftor MeSH Prohlížeč
- fixní kombinace léků MeSH
- indoly MeSH
- ivacaftor MeSH Prohlížeč
- protein CFTR MeSH
- pyrazoly MeSH
- pyridiny MeSH
- pyrrolidiny MeSH
- tezacaftor MeSH Prohlížeč
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.
Citace poskytuje Crossref.org
