Gene therapy

Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD). Clinical symptoms of CLI include rest pain, ischemic lesions/ulcers, and/or gangrene. Patients with CLI frequently end up having amputation and are at a very high risk of cardiovascular events, including death. Revascularization with angioplasty or bypass is the current standard of care for CLI. However, the treatment options for patients who are unsuitable for or fail revascularization attempts are extremely limited. Therapeutic angiogenesis is a novel strategy in the management of CLI. While the preclinical studies and phase I/II trials of therapeutic angiogenesis using gene and molecular-based therapies in patients with CLI showed promising results, outcomes of recent larger phase II/III studies have been inconsistent. However, as our understanding of the complex cellular and genetic mechanisms underlying angiogenesis, the experience with novel vectors and genetic targets, and preclinical and clinical trial design continue to get refined, the promise of therapeutic angiogenesis with gene therapy for CLI remains strong.