During this session we will explore novel and emerging approaches to overcome the basic physiological consequences of CFTR deficiency that do not directly target mutant CFTR proteins. These approaches have the potential to reduce disease burden in people with cystic fibrosis who currently are not responsive to CFTR modulator therapies. Considered will be potential therapeutic effects of recently discovered compounds targeting the epithelial sodium channel, sodium-hydrogen exchanger 3, the intracellular scaffold protein phosphoinositide 3-kinase Î³, and VPAC (vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide) receptors. In addition, a new pre-mRNA editing technique to remove disease-associated mutations by exon 15 skipping will be presented.
Analyze how compounds inhibiting the epithelial sodium channel and sodium-hydrogen exchanger 3 reverse the effects of CFTR deficiency on airway surface liquid hydration and mucus clearance.
Describe how polypeptides that either inhibit the intracellular scaffold protein phosphoinositide 3-kinase Î³ or have agonistic effects at VPAC (vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide) receptors increase channel function of F508del CFTR and reduce cystic fibrosis disease manifestations in mouse models.
Discuss a novel pre-mRNA editing technique to induce exon 15 skipping to remove an array of deleterious CFTR mutations in order to restore CFTR channel function.
Note: Speakers Patrick Moore, Alessandra Murabito, Valerie Chappe's presentations were not recorded at their request.