Korean J Med.  2003 Jan;64(1):85-90.

Vascular endothelial growth factor (VEGF)-induced angiogenic gene therapy in a patient with critical limb ischemia

• Kim HJ
• Jang SY
• Kim JM
• Kim SY
• Kim BM
• Kim WB
• Kim DK

Abstract

We report VEGF-induced angiogenic gene therapy in a patient with critical limb ischemia, who did not respond to conventional treatment. This patient was the first case in a dose-escalating series of phase I clinical trial. The patient had severe resting pain, gangrene and diffuse ulcer in his left foot. Total 1,000 micro gram of naked DNA encoding human VEGF165 was administered intramuscularly to 8 sites of the left lower extremity. Four weeks after the first 1,000 micro gram injection, a second 1,000 micro gram was administered to the same sites (total dose: 2,000 micro gram). After gene therapy, resting pain gradually reduced and the amount of analgesics taken by the patient decreased. The ischemic wound of lower extremity slightly improved. However, there was no complete wound healing at 12 weeks of treatment. Digital subtraction angiography at 12 weeks after gene therapy showed an increase in collateral vessels at the mid-tibial, ankle and foot arch levels. Immediately and up to 12 weeks, there was no complication related to gene therapy. These findings may be cautiously interpreted to indicate that intramuscular injection of naked plasmid DNA of VEGF165 may induce therapeutic angiogenesis in a patient with critical limb ischemia. Further clinical evaluation of VEGF-induced gene therapy is needed to evaluate the safety and efficiency of this treatment.

Keyword

Angiogenesis; Endothelial growth factors; Gene therapy; Peripheral vascular disease

MeSH Terms

Analgesics
Angiography, Digital Subtraction
Ankle
DNA
Endothelial Growth Factors
Extremities*
Foot
Gangrene
Genetic Therapy*
Humans
Injections, Intramuscular
Ischemia*
Lower Extremity
Peripheral Vascular Diseases
Plasmids
Ulcer
Vascular Endothelial Growth Factor A*
Wound Healing
Wounds and Injuries
Analgesics
DNA
Endothelial Growth Factors
Vascular Endothelial Growth Factor A