Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease

@article{Yang2008PhaseIC,
  title={Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease},
  author={Zhijian Yang and You-rong Zhang and Bo Chen and Shu-lan Zhang and En-Zhi Jia and Liansheng Wang and Tie-bing Zhu and Chun-jian Li and Hui Wang and Jun Huang and Ke-jiang Cao and Wen-zhu Ma and Bin Wu and Li-Sheng Wang and Chu-Tse Wu},
  journal={Molecular Biology Reports},
  year={2008},
  volume={36},
  pages={1323-1329}
}
Objective Therapeutic angiogenesis is a new strategy for treatment of vascular insufficiency. Hepatocyte growth factor (HGF)-induced angiogenesis has been applied to induce the neovascularization of ischemic adult tissues in preclinical studies. This report summarizes a phase I clinical trial on the safety of adenovirus-mediated human HGF (Ad-HGF) gene transfer to treat clinically significant coronary artery disease. Methods The 18 patients with severe and diffused triple vessel disease… 

Gene therapy to stimulate angiogenesis to treat diffuse coronary artery disease.

Overall, studies of gene therapy for ischemia in experimental models are very encouraging, with clear evidence of safety and efficacy, strongly supporting the concept that gene therapy to induce angiogenesis is a viable therapeutic approach for CAD.

Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

Intracoronary Ad-HGF administration is safe and potentially efficient in improving EF of patients with severe diffuse coronary disease in 3-year follow-up.

Long-term follow-up assessment of a phase 1 trial of angiogenic gene therapy using direct intramyocardial administration of an adenoviral vector expressing the VEGF121 cDNA for the treatment of diffuse coronary artery disease.

It is concluded that adenovirus-mediated VEGF direct myocardial administration to patients with severe coronary artery disease is safe, and future larger trials are warranted to assess efficacy.

Progress of Gene Therapy in Cardiovascular Disease

The recent advances in proangiogenic gene therapy for critical limb ischemia and DNA vaccine for hypertension are discussed.

Catheter-Based Intramyocardial Delivery (NavX) of Adenovirus Achieves Safe and Accurate Gene Transfer in Pigs

Intramyocardial injection guided by NavX system provides a method of feasible and safe percutaneous gene transfer to myocardial infarct regions and shows a positive effect in patients with severe and diffused triple coronary disease.

Effects of Adenovirus-Mediated Hepatocyte Growth Factor Gene Therapy on Postinfarct Heart Function: Comparison of Single and Repeated Injections.

It is concluded that fractional repeated injections of Ad-HGF may represent a promising therapeutic strategy to improve cardiac function in the setting of postinfarct heart failure.

HGF percutaneous endocardial injection induces cardiomyocyte proliferation and rescues cardiac function in pigs☆

Human Growth Factor/Immunoglobulin Complexes for Treatment of Myocardial Ischemia-Reperfusion Injury

The results suggest that human growth factor/IgG and FGF2/Fc- fusion complexes have potential to provide a biologics platform to treat myocardial ischemia-reperfusion and other forms of tissue injury.

Novel therapy for myocardial infarction: can HGF/Met be beneficial?

The mechanistic basis for autocrine and paracrine protection of HGF in the injured heart is described and the potential of the molecule for treating ischaemic heart disease in humans is discussed.

Angiogenic gene therapy in cardiovascular diseases: dream or vision?

The concept of angiogenic therapy as a sole treatment is re-evaluated and a combination with regenerative therapies or standard revascularization operations might be needed to improve tissue function and clinical benefits.
...

References

SHOWING 1-10 OF 26 REFERENCES

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Safety Evaluation of Clinical Gene Therapy Using Hepatocyte Growth Factor to Treat Peripheral Arterial Disease

The initial clinical outcome with HGF gene transfer seems to indicate usefulness as sole therapy for CLI and safe and feasible injection of naked HGF plasmid DNA is safe, feasible, and can achieve successful improvement of ischemic limbs.

Induction of collateral artery growth and improvement of post-infarct heart function by hepatocyte growth factor gene transfer

High expression levels of human HGF were observed in the myocardium because of non-infarct-related vessel transfer, which can increase the number of functional arterioles and improve collateral artery growth and heart function.

Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy

Overall, the present in vivo experiments demonstrated that intramyocardial injection of human HGF plasmid DNA in ischemic cardiomyopathy resulted in a significant improvement in cardiac function through an increase in blood flow and decrease in fibrosis, suggesting potential utility to treat patients with isChemic heart disease using HGF gene transfer.

Induction of Angiogenesis and Inhibition of Apoptosis by Hepatocyte Growth Factor Effectively Treats Postischemic Heart Failure

Overexpression of HGF 3 weeks post‐MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function.

Postinfarction Treatment With an Adenoviral Vector Expressing Hepatocyte Growth Factor Relieves Chronic Left Ventricular Remodeling and Dysfunction in Mice

Postinfarction HGF gene therapy improved LV remodeling and dysfunction through hypertrophy of cardiomyocytes, infarct wall thickening, preservation of vessels, and antifibrosis.

Therapeutic Angiogenesis: Protein and Gene Therapy Delivery Strategies

The techniques available for providing therapeutic angiogenesis are described, including acute and sustained-release techniques to deliver protein angiogens and a number of gene therapy strategies to deliver genes coding for the angiogenic processes.

Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease

Overall, intramuscular injection of naked human HGF plasmid induced therapeutic angiogenesis in rat and rabbit ischemic hindlimb models, as potential therapy for peripheral arterial disease.

Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor.