title: Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease.
abstract: 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 determined by coronary angiography, 1-3 of the main coronary arteries not amenable to bypassing grafting and to catheter-based revascularization were assigned to 3 study groups according to the dose of Ad-HGF (from low to high), and the total dose as follows: 5 x 10(9) pfu (group A, n = 6); 1 x 10(10) pfu (group B, n = 6); 2 x 10(10) pfu (group C, n = 6). Arterial gene transfer was performed by over-the wire balloon to the distal of the accessible artery or otherwise the ostium of the target vessels by diagnostic coronary catheter. General safety parameters and cardiac-specific parameters were measured through the preoperative period and on day 7, 21, and 35 postoperatively. The safety and tolerance of Ad-HGF for patients were evaluated according to functional and cytological assessments.
  
  
  RESULTS
  During the acute phase up to day 35 and at 11-14 months of follow-up there were no serious adverse events. A mild fever during the first 3 days was not present at day 4, and no long term or paroxysmal fever was found. There were no acute alterations in hemodynamic parameters and the electrocardiogram remained normal. No serious pericardial effusion was reported and there were no arrhythmia on Holter registrations. Moreover, the serum levels of HGF were not changed and the serum anti-adenovirus in the patients was not detected up to day 35.
  
  
  CONCLUSIONS
  The present study demonstrates that it is feasible to safely use an adenovirus gene-transfer vector to deliver the human hepatocyte growth factor gene to individuals with clinically significant coronary artery disease by direct intracoronary injection. However, a great deal of additional work must be done before administration of Ad-HGF can be recommended for clinical practice.
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, Jiangsu Province, People's Republic of China. enzhijia@yahoo.com.cn
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Yang
authors.forename: You-Rong
authors.initials: YR
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Zhang
authors.forename: En-Zhi
authors.initials: EZ
authors.lastname: Jia
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Wang
authors.forename: Tie-Bing
authors.initials: TB
authors.lastname: Zhu
authors.forename: Chun-Jian
authors.initials: CJ
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.forename: Ke-Jiang
authors.initials: KJ
authors.lastname: Cao
authors.forename: Wen-Zhu
authors.initials: WZ
authors.lastname: Ma
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wang
authors.forename: Chu-Tse
authors.initials: CT
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae; D000368:Aged; D000369:Aged, 80 and over; D002404:Catheterization; D003327:Coronary Disease / Q000150:complications / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012449:Safety; D016896:Treatment Outcome
chemical_list: D017228:Hepatocyte Growth Factor