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Hepatocyte growth factor as potential cardiovascular therapy
Hironori Nakagami1, Yasufumi Kaneda, Toshio Ogihara
1Division of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Expert Review of Cardiovascular Therapy
|May 14, 2005
Summary
Gene therapy using hepatocyte growth factor (HGF) plasmid safely improved blood flow and reduced ulcers in critical limb ischemia patients. This angiogenic factor shows promise for treating peripheral arterial disease and other ischemic conditions.
Area of Science:
- Regenerative Medicine
- Vascular Biology
- Gene Therapy
Background:
- Hepatocyte growth factor (HGF) is a pleiotropic factor regulating cell growth, motility, and morphogenesis.
- HGF acts as an angiogenic growth factor, promoting collateral artery development.
- HGF and its receptor c-met are present in vascular cells, suggesting a role in vascular health.
Purpose of the Study:
- To evaluate the angiogenic activity of HGF gene therapy in a preclinical model of peripheral arterial disease.
- To assess the safety and efficacy of intramuscular HGF plasmid DNA injection in patients with critical limb ischemia.
Main Methods:
- Preclinical study: Intramuscular injection of naked HGF plasmid into the ischemic hind limb of rabbits.
- Clinical trial: Prospective open-labeled trial involving six patients with critical limb ischemia (arteriosclerosis obliterans or Buerger disease).
- HGF plasmid DNA was administered via intramuscular injection into the ischemic limbs.
Main Results:
- HGF plasmid injection significantly augmented collateral vessel development in rabbits.
- Five out of six patients experienced pain reduction (>1 cm on visual analog scale).
- Five out of five patients showed an increased ankle pressure index (>0.1).
- Ischemic ulcer size decreased by >25% in 8/11 ulcers across four patients.
Conclusions:
- Intramuscular injection of naked HGF plasmid is safe, feasible, and improves ischemic limbs.
- HGF gene transfer shows potential as a monotherapy for critical limb ischemia.
- Further randomized, placebo-controlled trials are needed to define optimal dosing and efficacy.