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New and emerging targeted therapies for cystic fibrosis

Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70 000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a...

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Published in:BMJ (Online) 2016-03, Vol.352, p.i859-i859
Main Authors: Quon, Bradley S, Rowe, Steven M
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description Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70 000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development.
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The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. 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subjects Aminophenols - therapeutic use
Aminopyridines - therapeutic use
Antibiotics
Bacterial infections
Benzodioxoles - therapeutic use
Clinical Review
Clinical Trials as Topic
Cystic fibrosis
Cystic Fibrosis - genetics
Cystic Fibrosis - therapy
Cystic Fibrosis Transmembrane Conductance Regulator - drug effects
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - physiology
Drug Discovery - trends
Drug Therapy, Combination
Enzymes
Forced Expiratory Volume - drug effects
Forecasting
Genes
Genetic Therapy - methods
Genetic Therapy - trends
Homozygote
Humans
Inflammation
Kinases
Molecular Targeted Therapy - methods
Molecular Targeted Therapy - trends
Mutation
Mutation - genetics
Nitric oxide
Oxadiazoles - therapeutic use
Phosphodiesterase 5 Inhibitors - therapeutic use
Practice Guidelines as Topic
Precision Medicine - methods
Precision Medicine - trends
Proteins
Quinolones - therapeutic use
title New and emerging targeted therapies for cystic fibrosis
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