Focal angiogenic therapy for myocardial ischemia

Area of Science:

• Cardiovascular Medicine
• Regenerative Medicine
• Molecular Therapy

Background:

• Therapeutic angiogenesis aims to improve myocardial perfusion by stimulating collateral vessel formation.
• It is explored for patients with intractable angina unsuitable for conventional revascularization.
• Angiogenic cytokines are key to this treatment approach.

Purpose of the Study:

• To evaluate the safety and efficacy of angiogenic therapy, specifically gene therapy, for intractable angina.
• To describe the technical aspects of surgical gene therapy delivery.
• To assess the potential of angiogenic therapy as a novel revascularization modality.

Main Methods:

• Gene therapy involves DNA transfection for localized, prolonged exposure to angiogenic factors.
• Surgical delivery via mini thoracotomy incision is detailed.
• Phase I clinical trials were conducted, including studies using plasmid DNA for vascular endothelial growth factor-165 (VEGF165).

Main Results:

• Four Phase I trials reported, with two using gene therapy alone.
• The approach demonstrated relative safety with encouraging early efficacy.
• A study of 30 patients receiving VEGF165 plasmid DNA showed improvements in angina, exercise tolerance, and myocardial perfusion.

Conclusions:

• Preliminary results suggest angiogenic therapy is safe and potentially effective.
• Randomized clinical trials are necessary to compare angiogenic therapy with standard treatments or placebo.
• Ongoing trials explore catheter-based and combined surgical/gene therapy approaches for ischemic myocardium.