Double VEGF/HGF Gene Therapy in Critical Limb Ischemia Complicated by Diabetes Mellitus

Area of Science:

• Vascular Biology and Regenerative Medicine
• Gene Therapy Applications
• Diabetology

Background:

• Critical leg ischemia (CLI) is the advanced stage of peripheral arterial disease, often complicated by diabetes mellitus (DM).
• Standard treatments like antiplatelet drugs, statins, and revascularization are not suitable for all CLI patients.
• Gene therapy presents a promising alternative for patients ineligible for revascularization.

Purpose of the Study:

• To evaluate the efficacy of a dual vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) gene therapy.
• To assess the safety and effectiveness of this gene therapy in patients with CLI and DM.

Main Methods:

• Administration of a pIRES/VEGF165/HGF bicistronic plasmid.
• Evaluation of serum VEGF levels, ankle-brachial index (ABI), rest pain scores, and vascularization via computed tomography angiography (CTA).
• Comparison of outcomes between the treatment group and a control group over 90 days.

Main Results:

• Significant increases in serum VEGF levels and ABI (p < 0.001) were observed.
• A significant decrease in rest pain was noted compared to the control group (p < 0.002).
• Computed tomography angiography revealed considerable improvement in vascularization in the treated group (P = 0.04).

Conclusions:

• The pIRES/VEGF165/HGF bicistronic plasmid therapy is a safe and effective treatment for CLI patients with DM.
• This dual gene therapy approach shows potential for improving limb perfusion and alleviating pain in this patient population.
• Further research may validate gene therapy as a standard treatment for CLI complicated by diabetes.