Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial

Background We and others have previously reported significant changes in ch loride transport after cationic-lipid-mediated transfer of the cystic fibro sis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of th is gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial. Methods Eight patients with cystic fibrosis were randomly assigned DNA-lipi d complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protoc ol but with the lipid alone (placebo). Safety was assessed clinically, by r adiography, by pulmonary function, by induced sputum, and by histological a nalysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflu x, and bacterial adherence. Findings Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patien ts in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a sign ificant (p<0.05) degree of correction of the chloride abnormality in the pa tients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux. Bacterial adherence w as also reduced. We detected no alterations in the sodium transport abnorma lity. A similar pattern occurred following-nasal administration. Interpretation Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cys tic fibrosis.