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Case Reports
. 2021 Apr;9(4):e1656.
doi: 10.1002/mgg3.1656. Epub 2021 Mar 13.

Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype

Vito Terlizzi  1 , Felice Amato  2   3 , Chiara Castellani  1 , Beatrice Ferrari  1 , Luis J V Galietta  4   5 , Giuseppe Castaldo  2   3 , Giovanni Taccetti  1
Affiliations
Case Reports

Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype

Vito Terlizzi et al. Mol Genet Genomic Med. 2021 Apr.

Abstract

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.

Keywords: children; cystic fibrosis; lumacaftor/ivacaftor; nasal brushing.

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Conflict of interest statement

The authors have indicated they have no conflicts of interest relevant to this article to disclose.

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