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Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype

The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the...

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Autores principales: Comegna, Marika, Terlizzi, Vito, Salvatore, Donatello, Colangelo, Carmela, Di Lullo, Antonella Miriam, Zollo, Immacolata, Taccetti, Giovanni, Castaldo, Giuseppe, Amato, Felice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300667/
https://www.ncbi.nlm.nih.gov/pubmed/34356748
http://dx.doi.org/10.3390/antibiotics10070828
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author Comegna, Marika
Terlizzi, Vito
Salvatore, Donatello
Colangelo, Carmela
Di Lullo, Antonella Miriam
Zollo, Immacolata
Taccetti, Giovanni
Castaldo, Giuseppe
Amato, Felice
author_facet Comegna, Marika
Terlizzi, Vito
Salvatore, Donatello
Colangelo, Carmela
Di Lullo, Antonella Miriam
Zollo, Immacolata
Taccetti, Giovanni
Castaldo, Giuseppe
Amato, Felice
author_sort Comegna, Marika
collection PubMed
description The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. To date, these patients are excluded from treatment with Trikafta in Italy, where the CF patients carrying F508del/unknown represent about 1.3% (71 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment. This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine.
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spelling pubmed-83006672021-07-24 Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype Comegna, Marika Terlizzi, Vito Salvatore, Donatello Colangelo, Carmela Di Lullo, Antonella Miriam Zollo, Immacolata Taccetti, Giovanni Castaldo, Giuseppe Amato, Felice Antibiotics (Basel) Article The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. To date, these patients are excluded from treatment with Trikafta in Italy, where the CF patients carrying F508del/unknown represent about 1.3% (71 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment. This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine. MDPI 2021-07-07 /pmc/articles/PMC8300667/ /pubmed/34356748 http://dx.doi.org/10.3390/antibiotics10070828 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Comegna, Marika
Terlizzi, Vito
Salvatore, Donatello
Colangelo, Carmela
Di Lullo, Antonella Miriam
Zollo, Immacolata
Taccetti, Giovanni
Castaldo, Giuseppe
Amato, Felice
Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype
title Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype
title_full Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype
title_fullStr Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype
title_full_unstemmed Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype
title_short Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype
title_sort elexacaftor–tezacaftor–ivacaftor therapy for cystic fibrosis patients with the f508del/unknown genotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300667/
https://www.ncbi.nlm.nih.gov/pubmed/34356748
http://dx.doi.org/10.3390/antibiotics10070828
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