Henry Ford Health and Michigan State University Health Sciences received a USD 1.56 million NIH R01 grant from the National Heart, Lung, and Blood Institute to develop an inhaled formulation of vonoprazan for idiopathic pulmonary fibrosis — a disease with no curative therapy and a median survival of roughly three years after diagnosis.
The grant targets a significant unmet need. The two FDA-approved IPF treatments, pirfenidone (Esbriet) and nintedanib (Ofev), slow progression but do not reverse fibrosis or reduce mortality, leaving lung transplantation as the only definitive option for eligible patients. The research team, led by principal investigator Xiaopeng Li, is pursuing a drug repurposing strategy centered on ATP12A, a proton pump expressed in airway epithelium that acidifies the airway surface liquid. Preliminary data from IPF lung explants indicated elevated ATP12A expression in distal small airways compared with healthy tissue, and ATP12A overexpression in mice worsened bleomycin-induced fibrosis. The proposed mechanism links airway acidification to enhanced TGF-β1 activation and impaired mucociliary clearance — both drivers of fibrotic remodeling.
Vonoprazan is an established potassium-competitive acid blocker approved for gastric indications, but its oral pharmacokinetic profile — low bioavailability, poor solubility, and first-pass metabolism — limits achievable lung concentrations. The project aims to engineer an inhaled dry-powder formulation optimized for pulmonary delivery, with study aims covering aerosolization performance, pulmonary pharmacokinetics in mice, and efficacy testing in a humanized IPF mouse model.