ABSTRACT
Cystic fibrosis (CF) is a systemic disease that affects multiple organs due to malfunctioning of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF lung disease, however, is the main cause of morbidity and mortality of individuals with CF. CFTR dysfunction in the lungs causes an increased microbial burden that contributes to chronic airway inflammation and repetitive lung injury. CFTR functions as an anion channel that regulates ion and fluid homeostasis across various epithelia. Nonsense mutations in the CFTR gene generate premature termination codons in the mature messenger RNA. Development of small molecule therapies targeting F508-CFTR have mainly focused on the folding and processing defects of the protein Small molecule rescue of CFTR has and will probably remain mainly focused on the F508del-CFTR mutation, with the aim of identifying compound combinations that can restore F508del-CFTR function beyond the threshold associated with disease.
