AeroNeph Tx has a unique class of ‘coumarin derivatives’ that act as CFTR correctors/activators, ENaC inhibitors, and anti-proliferatives (cytostatic growth arresting drugs). For both forms of polycystic kidney disease (autosomal dominant PKD and autosomal recessive PKD), a CFTR corrector/activator will slow hyperproliferation of human cystic PKD cells and an ENaC inhibitor will attenuate hypertension that precedes cystic disease and renal decline in both ADPKD and ARPKD. A unique ENaC inhibitor will also be promising for rare genetic renal hypertensive disorders (Liddle’s syndrome, Bartter’s syndrome, Gitelman’s syndrome).
More recent evidence in the literature suggests that CFTR up-regulation and/or ENaC inhibition may be therapeutically beneficial for endocrine-driven cancers and chronic kidney disease (CKD), as well as both forms of PKD. And, as this chemical class of coumarin derivatives was found originally in a screen for CFTR correctors in CF human bronchial epithelial cells, this preclinical drug asset may also be therapeutic in cystic fibrosis (CF) and in related chronic lung diseases (chronic bronchitis within COPD and asthma). Multiple patents have been issued for this R&D program in two families related to the disease indications in focus. The cellular mechanism of action of the drug relates to PI3 kinase inhibition and modulation of microtubules, which serves to up-regulate CFTR trafficking to the cell surface and down-regulate ENaC by removal and trafficking from the cell surface.