Pitfalls of drug development: lessons learned from trials of denufosol in cystic fibrosis
RB Moss - The Journal of pediatrics, 2013 - jpeds.com
Richard B. Moss, MD The life-shortening genetic disease cystic fibrosis (CF) is caused by
mutations in the CF gene on both alleles, resulting in failure of a defective CF
transmembrane conductance regulator (CFTR) glycoprotein to normally regulate chloride
and bicarbonate flux at the airway surface. 1 According to a leading theory of CF
pathogenesis, the “volume depletion” hypothesis, this abnormal anion transport leads to
reduced airway surface liquid, airway dehydration, and impaired mucociliary clearance …
mutations in the CF gene on both alleles, resulting in failure of a defective CF
transmembrane conductance regulator (CFTR) glycoprotein to normally regulate chloride
and bicarbonate flux at the airway surface. 1 According to a leading theory of CF
pathogenesis, the “volume depletion” hypothesis, this abnormal anion transport leads to
reduced airway surface liquid, airway dehydration, and impaired mucociliary clearance …