In cystic fibrosis, lung function improves with therapy that targets specific molecular abnormalities in the cystic fibrosis transmembrane conductance regulator to increase the probability that this chloride channel is open.
These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established.
Small molecules that correct the folding defects and enhance surface localization of the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) comprise an important therapeutic strategy for cystic fibrosis lung disease.
The variability of cystic fibrosis lung disease and the variable expressivity of mild CFTR alleles complicate genetic counseling for this autosomal recessive disorder.
Emerging data indicate that non-CFTR genetic variants contribute to at least half the variability in pulmonary disease severity, and genetic variation in transforming growth factor beta1 clearly modifies the severity of cystic fibrosis lung disease.
Recombinant adenoviruses are being evaluated for gene therapy of cystic fibrosis lung disease with the goal of reconstituting the expression of the cystic fibrosis transmembrane conductance regulator in pulmonary epithelia by direct administration of the virus into the airway.