Human HGF plasmid DNA therapy
Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for
ischemic reperfusion injury after MI. The benefits of HGF therapy include preventing improper remodelling of the heart and ameliorating heart dysfunction post-MI.[1][3]
Human hepatocyte growth factor
Research and clinical trials
Animal research has demonstrated that administration of HGF
plasmids into ischemic cardiac tissue can increase cardiac function (improved left ventricular ejection fraction and fractional shortening compared to control subjects) after induced MI or ischemia.[6][3] Transfection with HGF plasmids in damaged cardiac tissue also promotes angiogenesis (increased capillary density compared to control subjects), as well as decreasing detrimental remodelling of the tissue at the site of injury (decreased fibrotic deposition).[4][6][7] The increased production of HGF by transfected cardiomyocytes during injury has also shown to be a powerful chemo-attractant of adult mesenchymal stem cells via HGF/c-Met binding.[4][5] The mitogenic and morphogenic properties of HGF induce recruited stem cells to take on cardiomyocyte phenotypes, potentially helping in the healing of ischemic tissue.[5]
The benefits of HGF in experimental models have led to its investigation in clinical trials. A adenovirus vector with the human HGF (Ad-hHGF) gene into the coronary vessels localized to ischemic tissue. Results demonstrate that it is in fact safe to administer the Ad-hHGF vector into patients with coronary artery disease in hopes of re-vascularizing damaged tissue in patients for which coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) are not available or possible. Despite the trial’s limitations (i.e. no assessment of left ventricular function and sample size was quite small), upon follow up assessments at 12 months, none of the patients receiving the treatment had been readmitted to hospital for MI, angina or aggravated heart failure.[1]