Short-term safety and curative effect of recombinant adenovirus carrying hepatocyte growth factor gene on ischemic cardiac disease.
BACKGROUND
Adenovirus-mediated angiogenic growth factor gene transfer provides a new therapeutic strategy for treatment of coronary heart disease. Preclinical studies showed that direct intramyocardial injection of recombinant adenovirus with hepatocyte growth factor gene (Ad-HGF) was able to promote neovascularization, improve heart function and abate the area of ischemic myocardia in animal models. However, the safety and therapeutic effect of Ad-HGF were not evaluated in clinical trials.


METHODS
A open-label, safety and tolerance trial of Ad-HGF in 18 patients suffering from coronary heart disease was performed. Three groups, each with 6 patients, received 5x10(8) (low dosage), 1.5 x 10(9) (medium dosage) and 5x10(9) (high dosage) pfu of Ad-HGF/person respectively, by direct multipoint injection into the myocardium while accepting coronary artery bypass surgery. The changes of vital symptoms, blood and urea routine analyses, as well as myocardial perfusion before and after treatment were analyzed.


RESULTS
There was no evidence of systemic or cardiac-related adverse events after intramyocardial administration of the Ad-HGF. Myocardial perfusion of the Ad-HGF-injected area was improved in 3 cases of the low-dose group, 5 cases of the medium-dose group, and all of the high-dose group.


CONCLUSIONS
These preliminary clinical data indicate that direct intramyocardial administration of Ad-HGF was well tolerated and could improve myocardial perfusion with a dose-effect relationship, encouraging larger and randomized efficacy trials.
Yuan
Biao
B
The First Affiliated Hospital of Nanjing Medical University, China.
Zhao
Zhong
Z
Zhang
You-Rong
YR
Wu
Chu-Tse
CT
Jin
Wei-Guo
WG
Zhao
Sheng
S
Wangl
Wei
W
Zhang
Yang-Yang
YY
Zhu
Xiao-Luan
XL
Wang
Li-Sheng
LS
Huang
Jun
J
D000256:Adenoviridae / Q000235:genetics*; D000368:Aged; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000628:therapy*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000009:adverse effects; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011995:Recombination, Genetic; D015899:Tomography, Emission-Computed, Single-Photon
D017228:Hepatocyte Growth Factor