Project 3: Treatment of mucostasis and airways obstruction in CF with a novel mucolytic

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PROJECT SUMMARY Mucus obstruction of airways is a significant pathologic feature of CF lung disease. Available therapies are only partially effective at relieving this obstruction, and additional treatments are needed. Gel-forming mucin molecules are a major constituent of CF mucus and to a large degree determines its bio-rheological properties. The development of inhaled agents that target mucin molecules and improve the transportability of airway mucus is a rational and attractive therapeutic goal. In this Project, we propose to first test the safety of a novel inhaled mucolytic in CF subjects in a single ascending dose study. We will then evaluate the ability of this agent to improve mucus clearance and reduce airways obstruction during two weeks of use, in a placebo controlled cross-over study in CF. Relevant, novel outcome measures will be utilized to evaluate drug effects on mucus clearance (gamma scintigraphy) and airways obstruction (19F-MRI with 1H-MRI/UTE), in addition to traditional clinical trial endpoints. The combination of these functional and structural modalities should greatly enhance our understanding of drug effects on this heterogeneous lung disease.