Yet a further way in which a pharmacological approach to CF can be considered is to recruit alternative chloride channels, such as calcium-activated chloride channel (CaCC), to act as surrogates for CFTR.
With the increasing knowledge of cystic fibrosis (CF) and CFTR-related diseases (CFTR-RD), the number of sequence variations in the CFTR gene is constantly raising.
With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator therapy, the clinical spectrum of this complex multisystem disease continues to evolve.
With the approval of promising small molecule correctors and potentiators, molecular characterization of Chinese-specific CFTR mutations will help to realize more precise treatment for Chinese CF patients.
With the advent of highly effective CF transmembrane conductance regulator modulators that are increasingly available, many individuals with CF now have significantly improved life expectancy.
With the adapted Fischer rat thyroid-yellow fluorescent protein halide flux assay to the combination high-throughput screening platform, we identified many interesting single agents as CFTR modulators from a library of approved drugs and mechanistic probe compounds, and combinations that synergistically modulate F508del-CFTR channel function in Fischer rat thyroid cells, demonstrating the potential for combination therapeutics to address the defects that cause CF.
With restoration of adequate CFTR function through pharmacotherapy, it is possible that the clinical course of patients with CF could be markedly improved, including longevity, quality of life and treatment burden.
With improvements in efficacy, manipulating the airway epithelium to make it permissive towards cell transplantation may provide another option for safe and effective correction of CF transmembrane conductance regulator function in CF airways.
With differentiated cystic fibrosis (CF) airway epithelia in vitro, a 20-min application of Ad:CaPi coprecipitates that encode CF transmembrane conductance regulator produced as much CF transmembrane conductance regulator Cl- current as a 24-h application of adenovirus alone.
With a view to assessing genotype-to-phenotype correlations in cystic fibrosis (CF), the clinical presentation of CF children from the United Arab Emirates (UAE) who were homozygous for cystic fibrosis transmembrane conductance regulator (CFTR) mutation S549R(T-->G was investigated.
While the safety and effectiveness remain to be demonstrated, these observations suggest the feasibility of in vivo CFTR gene transfer as therapy for the pulmonary manifestations of CF.
While all patients with cystic fibrosis (CF) have mutations in both CFTR alleles, often only one CFTR change is detected in patients with other lung disorders.
While a major target in cystic fibrosis (CF) research in recent years has been the development of corrector and potentiator drugs targeting the cystic fibrosis transmembrane conductance regulator (CFTR) protein, these therapies have not yet proven robust enough to replace or eliminate other therapies that have demonstrated improved health outcomes and quality of life in patients with CF.
Whereas some complex-glycosylated CFTR was often present in rectal biopsies of F508del homozygous subjects, no mature CFTR was detectable in CF lungs at the stage of terminal respiratory insufficiency.
Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis.
When normal CFTR cDNA was overexpressed via a retroviral vector in CF or normal airway epithelial cells or in mouse fibroblasts, the protein produced had an apparent molecular mass of about 180 kDa.
We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB.
We, therefore, set out to find small molecule binders of NBD1 and test whether it is possible to develop these molecules into potent binders that increase CFTR trafficking in CF-patient-derived human bronchial epithelial cells.