Congenital Absence of Vas Deferens (CAVD) represents a major cause of obstructive azoospermia and is mainly related to biallelic alteration of the CFTR gene, also involved in Cystic Fibrosis.
On average, we achieved 30%-50% allelic correction in UABCs and bronchial epithelial cells (HBECs) from 10 CF patients and observed 20%-50% CFTR function relative to non-CF controls in differentiated epithelia.
In addition, chronic inflammation characteristic of CF may contribute to growth failure via alteration in the GH-insulin-like growth factor 1 signaling and other changes in the growth plate. rhGH and new CFTR modulators may improve some growth parameters.
Pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for cystic fibrosis (CF), the commonest monogenic autosomal recessive disease, and CFTR-related disorders in infants and youth.
Cystic fibrosis (CF) results from deficient CF transmembrane conductance regulator (CFTR) protein activity leading to defective epithelial ion transport.
We applied an individualized combination of standardized and new CFTR functional bioassays for a patient referred to the Verona CF Center for evaluation after several episodes of acute pancreatitis.
In this review we focus on intestinal organoids as in vitro model for CF, enabling for CF disease classification, drug development and treatment optimization in a personalized manner, taking into account rare CFTR mutations and clinical heterogeneity among individuals with CF.
This article summarizes the milestones in the development of elexacaftor/ivacaftor/tezacaftor leading to this first approval for the treatment of cystic fibrosis in patients aged ≥ 12 years who have ≥ 1 F508del mutation in the CFTR gene.
Ivacaftor improved lung function during the double-blind and open-label treatment periods in patients with CF and CFTR mutations associated with residual CFTR function (ClinicalTrials.gov, NCT01685801).
Despite the prospect of regulatory approval of a CFTR-targeting therapy for most CF mutations, strenuous efforts are still needed to fully comprehend CFTR structure-and-function for the development of better drugs to enable people with CF to live full and active lives.
Protein kinase CK2 has been previously suggested as an important player in regulating CFTR functions and it has been proposed as a pharmacological target in a combinatory therapy to treat CF patients.
This review addresses variants at the CFTR locus itself and CFTR CREs, together with the outcomes of the latest modifier gene studies with respect to the different CF phenotypes.
Cystic Fibrosis (CF) is the most common monogenic autosomal recessive disease in Caucasians caused by pathogenic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator <i>(CFTR)</i> gene.
Cystic fibrosis (CF), also commonly referred to as mucoviscidosis, is a multigene related disorder, involving a defect in the CF transmembrane conductance regulator protein, with over 1,500 genes, being identified with the condition.
These include refractory CFTR variants (premature truncation codons, splice defects, large indels, severe missense mutations, and others) not addressed by available modulators, and access to leading-edge therapeutic compounds for patients with ultrarare forms of CF.
Future studies plan to evaluate short- and long-term clinical effectiveness and impact on infections, of the next generation of CFTR modulator therapy, the highly effective triple-combination therapy, for individuals with CF, homozygous or heterozygous for F508del.
Moreover, massive evidences show that defective CFTR gives rise to extracellular GSH level decrease and elevated glucose concentrations in airway surface liquid (ASL), thus encouraging lung infection by pathogens in the CF advancement.
Elexacaftor-tezacaftor-ivacaftor was efficacious in patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous CFTR modulator regimens were ineffective.