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Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis

Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protei...

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Detalles Bibliográficos
Autores principales: O’Reilly, Ruth, Elphick, Heather E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770629/
https://www.ncbi.nlm.nih.gov/pubmed/24039402
http://dx.doi.org/10.2147/DDDT.S30345
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author O’Reilly, Ruth
Elphick, Heather E
author_facet O’Reilly, Ruth
Elphick, Heather E
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description Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ∆F508) would allow 90% of the CF population to benefit from disease-modifying treatment.
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spelling pubmed-37706292013-09-13 Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis O’Reilly, Ruth Elphick, Heather E Drug Des Devel Ther Review Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ∆F508) would allow 90% of the CF population to benefit from disease-modifying treatment. Dove Medical Press 2013-08-30 /pmc/articles/PMC3770629/ /pubmed/24039402 http://dx.doi.org/10.2147/DDDT.S30345 Text en © 2013 O’Reilly and Elphick, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
O’Reilly, Ruth
Elphick, Heather E
Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis
title Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis
title_full Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis
title_fullStr Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis
title_full_unstemmed Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis
title_short Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis
title_sort development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770629/
https://www.ncbi.nlm.nih.gov/pubmed/24039402
http://dx.doi.org/10.2147/DDDT.S30345
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