Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype.
Aminophenols
/ administration & dosage
Aminopyridines
/ administration & dosage
Benzodioxoles
/ administration & dosage
Cells, Cultured
Child, Preschool
Chloride Channel Agonists
/ administration & dosage
Chlorides
/ metabolism
Cystic Fibrosis
/ drug therapy
Cystic Fibrosis Transmembrane Conductance Regulator
/ genetics
Epithelial Cells
/ drug effects
Female
Genotype
Humans
Mutation, Missense
Nasal Mucosa
/ cytology
Pancreatic Elastase
/ metabolism
Quinolones
/ administration & dosage
children
cystic fibrosis
lumacaftor/ivacaftor
nasal brushing
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
15
01
2021
received:
17
11
2020
accepted:
19
02
2021
pubmed:
14
3
2021
medline:
15
12
2021
entrez:
13
3
2021
Statut:
ppublish
Résumé
New drugs that target the basic defect in cystic fibrosis (CF) patients may now be used in a large number of patients carrying responsive mutations. Nevertheless, further research is needed to extend the benefit of these treatments to patients with rare mutations that are still uncharacterized in vitro and that are not included in clinical trials. For this purpose, ex vivo models are necessary to preliminary assessing the effect of CFTR modulators in these cases. We report the clinical effectiveness of lumacaftor/ivacaftor therapy prescribed to a CF child with a rare genetic profile (p.Phe508del/p.Gly970Asp) after testing the drug on nasal epithelial cells. We observed a significant drop of the sweat chloride value, as of the lung clearance index. A longer follow-up period is needed to define the effects of therapy on pancreatic status, although an increase of the fecal elastase values was found. Drug response obtained on nasal epithelial cells correlates with changes in vivo therapeutic endpoints and can be a predictor of clinical efficacy of novel drugs especially in pediatric patients.
Sections du résumé
BACKGROUND
New drugs that target the basic defect in cystic fibrosis (CF) patients may now be used in a large number of patients carrying responsive mutations. Nevertheless, further research is needed to extend the benefit of these treatments to patients with rare mutations that are still uncharacterized in vitro and that are not included in clinical trials. For this purpose, ex vivo models are necessary to preliminary assessing the effect of CFTR modulators in these cases.
METHOD
We report the clinical effectiveness of lumacaftor/ivacaftor therapy prescribed to a CF child with a rare genetic profile (p.Phe508del/p.Gly970Asp) after testing the drug on nasal epithelial cells. We observed a significant drop of the sweat chloride value, as of the lung clearance index. A longer follow-up period is needed to define the effects of therapy on pancreatic status, although an increase of the fecal elastase values was found.
CONCLUSION
Drug response obtained on nasal epithelial cells correlates with changes in vivo therapeutic endpoints and can be a predictor of clinical efficacy of novel drugs especially in pediatric patients.
Identifiants
pubmed: 33713579
doi: 10.1002/mgg3.1656
pmc: PMC8123755
doi:
Substances chimiques
Aminophenols
0
Aminopyridines
0
Benzodioxoles
0
CFTR protein, human
0
Chloride Channel Agonists
0
Chlorides
0
Quinolones
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
ivacaftor
1Y740ILL1Z
Pancreatic Elastase
EC 3.4.21.36
lumacaftor
EGP8L81APK
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1656Informations de copyright
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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