Gene transfer to induce angiogenesis in myocardial and limb ischaemia

Stimulation of angiogenesis/arteriogenesis by gene transfer methods offers hope for treating patients with myocardial and peripheral limb ischaemia who are not candidates for standard revascularisation procedures. Preclinical studies showed that adenoviral and plasmid vectors encoding various angiogenic cytokines were capable of inducing functionally significant angiogenesis in vitro and in animal models of chronic myocardial ischaemia. Early clinical studies using VEGF121-, FGF-4- and VEGF165-encoding vectors showed a reasonable safety profile with promising results. However, significant advances in vector technology including regulatable and longer-term expression, delivery strategies (local and organ/tissue specific), clinical trial design, and outcome measure development are needed before this investigational treatment becomes reality.