Ivacaftor treatment of cystic fibrosis patients with the G551D mutation: a review of the evidence

Kotha, Kavitha; Clancy, John

doi:10.1177/1753465813502115

Cited by 33 publications

(25 citation statements)

References 52 publications

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“…Specifically, ivacaftor (Kalydeco) is targeted to patients with at least 1 copy of a specific type of mutation, called a gating mutation, which results in improper regulation of the ion channel (such as G551D) (14)(15)(16)(17)(18)(19). In many cases, this regulation is restored, and patients have had remarkable improvements in lung and pancreatic function.…”

Section: Introductionmentioning

confidence: 99%

Nasospheroids permit measurements of CFTR-dependent fluid transport

Guimbellot¹,

Leach²,

Chaudhry³

et al. 2017

JCI Insight

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Section: Introductionmentioning

confidence: 99%

Nasospheroids permit measurements of CFTR-dependent fluid transport

Guimbellot¹,

Leach²,

Chaudhry³

et al. 2017

JCI Insight

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“…Organisms such as Streptococcus pnuemoniae and Staphylococcus aureus create a complex pulmonary niche and microbiome 6,7 . In the end, despite new developments in small molecular correctors and CFTR expression enhancers, the ensuing inflammatory response and pulmonary failure continue to be a serious issue leading to significant morbidity and eventual mortality in CF 8 . This is mostly due to the immune response in CF individuals which is too aggressive, and ultimately contributing to lung damage.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell Soluble Mediators and Cystic Fibrosis

Sutton

Fletcher

Episalla

et al. 2017

J Stem Cell Res Ther

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Human Mesenchymal stem cells (hMSCs) secrete products (supernatants) that are anti-inflammatory and antimicrobial. We have previously shown that hMSCs decrease inflammation and Pseudomonas aeruginosa infection in the in vivo murine model of Cystic Fibrosis (CF). Cystic Fibrosis (CF) is a genetic disease in which pulmonary infection and inflammation becomes the major cause of morbidity and mortality. Our studies focus on determining how MSCs contribute to improved outcomes in the CF mouse model centering on how the MSCs impact the inflammatory response to pathogenic organisms. We hypothesize that MSCs secrete products that are anti-inflammatory in scenarios of chronic pulmonary infections using the murine model of infection and inflammation with a specific interest in Pseudomonas aeruginosa (gram negative). Further, our studies will identify whether the MSCs are impacting this inflammatory response through the regulation of peroxisome proliferator activator receptor gamma (PPARγ) which aides in decreasing inflammation.

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“…Mutations causing CFTR dysfunction lead to cystic fibrosis (CF), a genetic disease common in Europe, USA, and other populations of European origin [1]. CF represents a severe affliction for which palliative treatment has been the only option, with the recent exception of Ivacaftor, a drug that improves CFTR function in patients with the G551D mutation [2]. Ivacaftor shows promise for other channel gating mutations as well, but only 4–5% of CF patients harbor these gating mutations [3].…”

Section: Introductionmentioning

confidence: 99%

A survey of detergents for the purification of stable, active human cystic fibrosis transmembrane conductance regulator (CFTR)

Hildebrandt

Zhang

Cant

et al. 2014

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Structural knowledge of the cystic fibrosis transmembrane conductance regulator (CFTR) requires developing methods to purify and stabilize this aggregation-prone membrane protein above 1 mg/ml. Starting with green fluorescent protein- and epitope-tagged human CFTR produced in mammalian cells known to properly fold and process CFTR, we devised a rapid tandem affinity purification scheme to minimize CFTR exposure to detergent in order to preserve its ATPase function. We compared a panel of detergents, including widely used detergents (maltosides, neopentyl gycols (MNG), C12E8, lysolipids, Chaps) and innovative detergents (branched alkylmaltosides, facial amphiphiles) for CFTR purification, function, monodispersity and stability. ATPase activity after reconstitution into proteoliposomes was 2–3 times higher when CFTR was purified using facial amphiphiles. ATPase activity was also demonstrated in purified CFTR samples without detergent removal using a novel lipid supplementation assay. By electron microscopy, negatively stained CFTR samples were monodisperse at low concentration, and size exclusion chromatography showed a predominance of monomer even after CFTR concentration above 1 mg/ml. Rates of CFTR aggregation quantified in an electrophoretic mobility shift assay showed that detergents which best preserved reconstituted ATPase activity also supported the greatest stability, with CFTR monomer half-lives of 6–9 days in MNG or Chaps, and 12–17 days in facial amphiphile. Cryoelectron microscopy of concentrated CFTR in MNG or facial amphiphile confirmed mostly monomeric protein, producing low resolution reconstructions in conformity with similar proteins. These protocols can be used to generate samples of pure, functional, stable CFTR at concentrations amenable to biophysical characterization.

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Ivacaftor treatment of cystic fibrosis patients with the G551D mutation: a review of the evidence

Cited by 33 publications

References 52 publications

Nasospheroids permit measurements of CFTR-dependent fluid transport

Nasospheroids permit measurements of CFTR-dependent fluid transport

Mesenchymal Stem Cell Soluble Mediators and Cystic Fibrosis

A survey of detergents for the purification of stable, active human cystic fibrosis transmembrane conductance regulator (CFTR)

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