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Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis
Cystic fibrosis (CF) is an autosomal recessive genetic condition that is caused by variants in the cystic fibrosis transmembrane conductance regulator gene. This causes multisystem disease due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel at the apical...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828078/ https://www.ncbi.nlm.nih.gov/pubmed/35153502 http://dx.doi.org/10.2147/PGPM.S245603 |
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author | Haq, Iram Almulhem, Maryam Soars, Simone Poulton, David Brodlie, Malcolm |
author_facet | Haq, Iram Almulhem, Maryam Soars, Simone Poulton, David Brodlie, Malcolm |
author_sort | Haq, Iram |
collection | PubMed |
description | Cystic fibrosis (CF) is an autosomal recessive genetic condition that is caused by variants in the cystic fibrosis transmembrane conductance regulator gene. This causes multisystem disease due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel at the apical surface of epithelia. Until recently, treatment was directed at managing the downstream effects in affected organs, principally improving airway clearance and treating infection in the lungs and improving malabsorption in the gastrointestinal tract. Care delivered by multidisciplinary teams has yielded incremental improvements in outcomes. However, the development of small-molecule CFTR modulator drugs over the last decade has heralded a new era of CF therapeutics. Modulators target the underlying defect and improve CFTR function. Either monotherapy or a combination of modulators is used depending on the specific genotype and class of CFTR disease-causing variants that an individual has. Both ivacaftor and the ivacaftor/tezacaftor/elexacaftor combination have been demonstrated to be associated with clinically very significant benefits in randomised trials and have rapidly been made available as part of standard care in many countries. CFTR modulators represent one of the best examples of precision medicine to date. They are expensive, however, and equity of access to them worldwide remains an issue. Studies and approvals are also ongoing for children under the age of 6 years for ivacaftor/tezacaftor/elexacaftor. Furthermore, no modulators are available for around 10% of the people with CF. In this review, we firstly summarise the genetics, pathophysiology and clinical problems associated with CF. We then discuss the development of CFTR modulators and key clinical trials to support their use along with other potential future therapeutic approaches. |
format | Online Article Text |
id | pubmed-8828078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-88280782022-02-11 Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis Haq, Iram Almulhem, Maryam Soars, Simone Poulton, David Brodlie, Malcolm Pharmgenomics Pers Med Review Cystic fibrosis (CF) is an autosomal recessive genetic condition that is caused by variants in the cystic fibrosis transmembrane conductance regulator gene. This causes multisystem disease due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel at the apical surface of epithelia. Until recently, treatment was directed at managing the downstream effects in affected organs, principally improving airway clearance and treating infection in the lungs and improving malabsorption in the gastrointestinal tract. Care delivered by multidisciplinary teams has yielded incremental improvements in outcomes. However, the development of small-molecule CFTR modulator drugs over the last decade has heralded a new era of CF therapeutics. Modulators target the underlying defect and improve CFTR function. Either monotherapy or a combination of modulators is used depending on the specific genotype and class of CFTR disease-causing variants that an individual has. Both ivacaftor and the ivacaftor/tezacaftor/elexacaftor combination have been demonstrated to be associated with clinically very significant benefits in randomised trials and have rapidly been made available as part of standard care in many countries. CFTR modulators represent one of the best examples of precision medicine to date. They are expensive, however, and equity of access to them worldwide remains an issue. Studies and approvals are also ongoing for children under the age of 6 years for ivacaftor/tezacaftor/elexacaftor. Furthermore, no modulators are available for around 10% of the people with CF. In this review, we firstly summarise the genetics, pathophysiology and clinical problems associated with CF. We then discuss the development of CFTR modulators and key clinical trials to support their use along with other potential future therapeutic approaches. Dove 2022-02-05 /pmc/articles/PMC8828078/ /pubmed/35153502 http://dx.doi.org/10.2147/PGPM.S245603 Text en © 2022 Haq et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Review Haq, Iram Almulhem, Maryam Soars, Simone Poulton, David Brodlie, Malcolm Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis |
title | Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis |
title_full | Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis |
title_fullStr | Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis |
title_full_unstemmed | Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis |
title_short | Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis |
title_sort | precision medicine based on cftr genotype for people with cystic fibrosis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828078/ https://www.ncbi.nlm.nih.gov/pubmed/35153502 http://dx.doi.org/10.2147/PGPM.S245603 |
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