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Cystic Fibrosis
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TLDR
Advances in understanding and treatment of cystic fibrosis are summarized, focusing on pulmonary disease, which accounts for most morbidity and deaths.Abstract:
Cystic fibrosis is the most common autosomal recessive disorder in white people, with a frequency of about 1 in 2500 livebirths. Discovery of the mutated gene encoding a defective chloride channel in epithelial cells--named cystic fibrosis transmembrane conductance regulator (CFTR)--has improved our understanding of the disorder's pathophysiology and has aided diagnosis, but has shown the disease's complexity. Gene replacement therapy is still far from being used in patients with cystic fibrosis, mostly because of difficulties of targeting the appropriate cells. Life expectancy of patients with the disorder has been greatly increased over past decades because of better notions of symptomatic treatment strategies. Here, we summarise advances in understanding and treatment of cystic fibrosis, focusing on pulmonary disease, which accounts for most morbidity and deaths.read more
Citations
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Journal ArticleDOI
Atomic Structure of the Cystic Fibrosis Transmembrane Conductance Regulator
Zhe Zhang,Jue Chen +1 more
TL;DR: The structure of zebrafish CFTR in the absence of ATP is determined by electron cryo-microscopy to 3.7 Å resolution and reveals why many cystic-fibrosis-causing mutations would lead to defects either in folding, ion conduction, or gating and suggests new avenues for therapeutic intervention.
Journal ArticleDOI
VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1.
Hong Yu Ren,Diane E. Grove,Oxana Adolfovna de la Rosa,Scott A. Houck,Pattarawut Sopha,Fredrick Van Goor,Beth Jennifer Hoffman,Douglas M. Cyr +7 more
TL;DR: VX-808 is able to partially restore function to F508del-CFTR and other disease-related mutants by modulating the conformation of membrane-spanning domain 1 in CFTR.
Journal ArticleDOI
Physiology of sweat gland function: The roles of sweating and sweat composition in human health
TL;DR: The role of sweating to eliminate waste products and toxicants seems to be minor compared with other avenues of excretion via the kidneys and gastrointestinal tract; as eccrine glands do not adapt to increase excretion rates either via concentrating sweat or increasing overall sweating rate.
Journal ArticleDOI
Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression
Guido Veit,Radu G. Avramescu,Doranda Perdomo,Puay Wah Phuan,Miklós Bagdány,Pirjo M. Apaja,Florence Borot,Daniel Szollosi,Yu Sheng Wu,Walter E. Finkbeiner,Tamás Hegedus,Tamás Hegedus,Alan S. Verkman,Gergely L. Lukacs +13 more
TL;DR: Combining the two types of drugs does not work effectively because potentiators make CFTR less stable, accelerating the removal of this channel from the cell membrane, suggesting the need for further optimization of potentiator to maximize the clinical benefit of corrector-potentiator combination therapy in CF.
Journal ArticleDOI
Repeated aerosolized AAV-CFTR for treatment of cystic fibrosis: a randomized placebo-controlled phase 2B trial.
Richard B. Moss,Carlos Milla,John L. Colombo,Frank J. Accurso,Pamela L. Zeitlin,John P. Clancy,L. Terry Spencer,Joseph M. Pilewski,David A. Waltz,Henry L. Dorkin,Thomas W. Ferkol,Mark Pian,Bonnie W. Ramsey,Barrie J. Carter,Dana B. Martin,Alison E. Heald +15 more
TL;DR: Repeat doses of aerosolized tgAAVCF were safe and well tolerated, but did not result in significant improvement in lung function over time, and further research is warranted to develop an effective gene transfer agent for the treatment of CF.
References
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Journal ArticleDOI
Modifier genes in cystic fibrosis lung disease.
TL;DR: It is now clear that CFTR genotype alone does not account for the wide diversity in CF pulmonary phenotype and evidence is accumulating that secondary genetic factors separate from the CFTR locus significantly influence the severity of CF lung disease.
Related Papers (5)
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation
Bonnie W. Ramsey,Jane C. Davies,N. Gerard McElvaney,Elizabeth Tullis,Scott C. Bell,Pavel Dř evínek,Matthias Griese,Edward F. McKone,Claire E. Wainwright,Michael W. Konstan,Richard B. Moss,Felix Ratjen,Isabelle Sermet-Gaudelus,Steven M. Rowe,Qunming Dong,Sally Rodriguez,Karl Yen,Claudia L. Ordoñez,J. Stuart Elborn +18 more