There was no difference in phagolysosomal pH between healthy control and CF macrophages (5.41 ± 0.11 vs. 5.41 ± 0.20, p > .9999), further confirmed by inhibiting Cystic Fibrosis Transmembrane Conductance Regulator in healthy control monocyte-derived macrophages.
ASO treatment further increased CFTR function in almost all CF genotypes tested on top of treatment with the FDA approved drug Symdeko (ivacaftor and tezacaftor).
The airway surface liquid height is regulated by transpeithelial Na<sup>+</sup> absorption (ENaC) and Cl<sup>-</sup> secretion (CFTR) in normal airway but mainly by ENaC activity in CF epithelia when Cl<sup>-</sup> secretion is compromised by CFTR mutations.
Traditionally, CF has been symptomatically managed, but over the past 6 years those with CF have been offered a new mode of therapy; CFTR protein modulation.
Owing to similarities between chronic bronchitis and the autosomal-recessive disease Cystic Fibrosis (CF), a significant body of research addresses the hypothesis that dysfunctional CF Transmembrane Conductance Regulator (CFTR) is implicated in the pathogenesis of COPD.
Acute Recurrent and Chronic Pancreatitis as Initial Manifestations of Cystic Fibrosis and Cystic Fibrosis Transmembrane Conductance Regulator-Related Disorders.
Importantly, stimulation of CFTR function with a pharmacological potentiator (Ivacaftor), which is approved for the treatment of CF, could attenuate the autophagy-inhibition and pro-inflammatory effects of gliadin in preclinical models of CD.
We have already seen some success in paediatrics in targeted therapies such as cystic fibrosis for specific cystic fibrosis transmembrane conductance regulator variants.
In vitro, eluforsen improved chloride efflux in CF pancreatic adenocarcinoma cell cultures and increased short-circuit current in primary human bronchial epithelial cells, both indicating restoration of CFTR function.
Because small synthetic transmembrane anion transporters (anionophores) can replace the biological anion transport mechanisms, independent of genetic mutations in the CFTR, such anionophores are candidates as new potential treatments for CF.
We use multi-DDM to assess the efficacy of different CFTR-modulating drugs in human airway epithelial cells derived from subjects with cystic fibrosis (ΔF508/ΔF508 and ∆F508/-) based on ciliary beat frequency and coordination.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel central to the development of secretory diarrhea and cystic fibrosis.
Our results suggest that CFTR dysfunction associates with an enhanced sphingolipid metabolism leading to the release of EVs that export the excess of pro-inflammatory Cer to the recipient cells, thus contributing to maintain the unresolved inflammatory status of CF.
This unexpected interface rearrangement is likely to have major relevance for CF pathogenesis but also for the normal function of CFTR and other ABC proteins.
The unusual kinetics of phagosomal HOCl production in CF neutrophils confirm a role for the cystic fibrosis transmembrane conductance regulator in maintaining HOCl production in neutrophil phagosomes.