The European Society of Gene and Cell Therapy, Madrid, 2013
Cystic fibrosis (CF) is the most common lethal inherited disease of Caucasian populations, affecting ~80,000 individuals worldwide. CF individuals, homozygous for mutations in the CFTR gene, suffer from repeated bacterial infections of the conducting airways that ultimately lead to lung failure and death.
The UK Cystic Fibrosis Gene Therapy Consortium (UKCFGTC) have previously demonstrated proof-of-principle for CFTR gene replacement therapy –correcting the CF chloride channel defect for ~1 week in patients receiving non-viral vectors. Our most advanced vector system is a non-viral gene transfer vector termed pGM169/GL67A.
This system comprises an entirely CG dinucleotide-free plasmid DNA (pGM169) that directs sustained CFTR lung expression in animal models, and a cationic liposome mixture (GL67A) the most effective non-viral lung gene transfer agent we identified from a large in vivo screen.
Following successful nonclinical toxicology studies, two clinical studies have been initiated. In an open-label Phase I/IIa study we have shown that a single dose to the nose and lungs of CF patients was safe and corrected the CF chloride channel defect for up to 3 months.
We have subsequently initiated a double-blinded, placebo controlled, Phase IIb study enrolling 130 CF patients, randomised 1:1 active:placebo, in which pGM169/GL67A is repeatedly (once a month for 1 year) delivered by aerosol to the lungs of CF patients.