A PLACEBO-CONTROLLED STUDY OF LIPOSOME-MEDIATED GENE-TRANSFER TO THE NASAL EPITHELIUM OF PATIENTS WITH CYSTIC-FIBROSIS

Cystic fibrosis (CF) is a common, serious, inherited disease. major ca use of mortality in CF is lung disease, to the failure of airway epith elial cells to express a product of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A potential treatment for CF lung d isease is the expression of CFTR in the airways following gene transfe r. We have undertaken a double-blinded, placebo-controlled, clinical s tudy of the transfer of the CFTR cDNA to the nasal epithelium of 12 CF patients. Cationic liposomes complexed with plasmid containing the hu man CFTR cDNA were administered to eight patients, whilst four patient s received placebo. Biopsies of the nasal epithelium taken 7 days afte r dosing were normal. No significant changes in clinical parameters we re observed Functional expression of CFTR assessed by in vivo nasal po tential difference measurements showed transient correction of the CF chloride transport abnormality in two patients (15 days after dosing i n one patient). Fluorescence microscopy demonstrated CFTR function ex vivo in cells from nasal brushings. In total, evidence of functional C FTR gene transfer was obtained in six out of the eight treated patient s. These results provide proof of concept for liposome-mediated CF gen e transfer.