SPX-101 Is a Promising and Novel Nebulized ENaC Inhibitor

Optimal hydration of the airway lumen is required for effective mucociliary clearance of inhaled pathogens and particulate matter (1). Because the airway epithelium is relatively permeable to water, the volume and composition of the airway surface liquid (ASL) is determined by active ion transport. In addition to this secretory deficit, the CF airway is hyperabsorptive as a result of dysregulated epithelial sodium channel (ENaC) activity (2-4). Because of these ion transport defects, the airway in CF is exceptionally vulnerable to dehydration, and the luminal contents are abnormally acidic and tenacious. [...]mucus clearance from the CF airway is reduced and causes chronic airway inflammation, obstruction, infection, and ultimately premature respiratory failure.