Study design (if review, criteria of inclusion for studies)
double-blind, placebo-controlled, rising-dose tolerance study
Participants
11 adult CF patients were studied
Interventions
cationic liposome [p-ethyl-dimyristoylphosphadityl choline (EDMPC) cholesterol] complexed with an expression plasmid containing hCFTR cDNA and placebo were sprayed into alternate nostrils at intervals over 7 h.
Outcome measures
safety and efficacy
Main results
After dosing, vector-specific DNA was present in nasal lavage of all subjects for up to 10 days. There were no adverse events. The vector-treated epithelium did not exhibit a significant increase in CFTR-mediated Cl- conductance from baseline and was not different from the placebo-treated nostril: mean deltaCFTR Cl- conductance, mV +/- SEM, -1.6+/-0.4 vs -0.6+/-0.4, respectively. CFTR-mediated Cl- conductance increased toward normal during repetitive nasal potential difference measurements over the 3 days before dosing which influenced the postdosing calculations. No vector-specific mRNA was detected in the nasal epithelial scrape biopsies, although endogenous CFTR mRNA was detected in all subjects.
Authors' conclusions
lipid-DNA complex is safe, but did not produce consistent evidence of gene transfer to the nasal epithelium by physiologic or molecular measures.
Keywords: Adult; Gene Transfer Techniques; non pharmacological intervention - genetic& reprod; pharmacological_intervention;