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Rapid therapeutic advances in CFTR modulator science

Clancy, John P.·2018·Pediatric Pulmonology
DOI 10.1002/ppul.24157PMC PMC6585954
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Abstract

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by variants in the gene encoding the cystic fibrosis transmembrane conduction regulator (CFTR) protein. Loss of CFTR function disrupts chloride, bicarbonate and regulation of sodium transport, producing a cascade of mucus obstruction, inflammation, pulmonary infection, and ultimately damage in numerous organs. Established CF therapies treat the downstream consequences of CFTR dysfunction and have led to steady improvements in patient survival. A class of drugs termed CFTR modulators has recently entered the CF therapeutic landscape. These drugs differ fundamentally from prior therapies in that they aim to improve the function of disease‐causing CFTR variants. This review summarizes the science behind CFTR modulators, including their targets, mechanism of action, clinical benefit, and future directions in the field. CFTR modulators have dramatically changed how CF is treated, validated CFTR as a therapeutic target, and opened the door to truly personalized therapies and treatment regimens.

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  • The efficacy outcomes confirm the hypothesis that elexacaftor-tezacaftor-ivacaftor effectively modulates the function of Phe508del CFTR from a single allele, providing pronounced benefits in a population of patients in whom previous CFTR modulator therapies were not effective.

    “The efficacy outcomes confirm the hypothesis that elexacaftor–tezacaftor–ivacaftor effectively modulates the function of Phe508del CFTR from a single allele, providing pronounced benefits in a population of patients in whom previous CFTR modulator therapies were not effective.15,19”

    From Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele (2019) · cites this paper as [19]

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Authors
Clancy, J. P.
Affiliations
Department of Pediatrics Cincinnati Childrens Hospital Medical Center Cincinnati Ohio
ORCID
Clancy, John P.
Venue
Pediatric Pulmonology
Publisher
Wiley
Published
2018-10-05
Volume
53
Issue
S3
ISSN
  • 8755-6863
  • 1099-0496
DOI
10.1002/ppul.24157
PMC
PMC6585954
Cited by
38
References
1
Language
en
Licence
creativecommons.org/licenses/by-nc/4.0/ (vor)
Funders
Cystic Fibrosis Foundation (CLANCY15X0)

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