Gene therapy for peripheral arterial disease using sendai virus vector: From preclinical studies to the phase I/IIa clinical trial

Great potential for limb salvaging with basic fibroblast growth factor (FGF-2) expressed from a Sendai virus vector with the full-length viral genome (SeV/FGF-2) in the target muscle was demonstrated in animal models of severe limb ischemia. The exogenously expressed FGF-2 induced other endogenous angiogenic factors, including vascular endothelial growth factor and hepatocyte growth factor in a highly concerted fashion, and this was shown to underlie the remarkable limb salvaging. These results led to the initiation of a phase I/IIa clinical trial for peripheral arterial disease (PAD) of humans. To be better prepared for unforeseen adverse events, this clinical trial used the F gene-deleted, nontransmissible, and hence safer (than SeV/FGF-2) version that carried the human FGF-2 gene (ΔFSeV/FGF-2; product code, DVC1-0101). Overall, DVC1-0101 appeared to be safe, giving rise to no serious adverse events in various criteria. Moreover, it exerted a significant therapeutic effect from a number of clinical aspects. DVC1-0101 represents the first case of the potential diverse medical applications of SeV vector. It is now hoped to move on to an advanced phase of clinical trial with a larger number of patients and placebo group to firmly establish the safety and efficacy of DVC1-0101.