Summary of Research Project Results under JSPS FY2003
"Research for the Future Program"

1.Research Institution Osaka University
2.Research Area Life Sciences
3.Research Field Angiogenesis and Vascular Development Control
4.Term of Project FY 1999 - FY 2003
5.Project Number 99L01303
6.Title of Project Development of New Therapeutics Using Angiogenesis and Regeneration of Endothelial Cells

7.Project Leader
Name Institution,Department Title of Position
Ryuichi, Morishita Osaka University, Graduate School of Medicine Professor

8.Core Members

9.Summary of Research Results

In this project, we confirmed that trans-gene of HGF induced angiogenesis and has beneficial effect on ischemic diseases in animal model. Based on such basic experiments, we planned clinical gene therapy for peripheral arterial diseases (PAD) and have performed [Japan Trial to Treat Peripheral Arterial Disease by Therapeutic Angiogenesis Using Hepatocyte Growth Factor Gene Transfer : TREAT-HGF] since May 2001. Currently, severe adverse effects related to gene transfection could not be detected in any patient. Also, we observed a beneficial effect (improvement of some clinical parameters) in 60 % of all patients received gene therapy. It would be expected that genomic medicine is newly developed in near future. Moreover, we evaluated the effect of trans-gene of HGF on ischemic heart model of porcine. Injection of HGF gene by NOGA catheter system resulted in the reduction of ischemic area and increase in blood supply. The provided data suggested the application of HGF-based gene therapy to ischemic heart disease and we are planning clinical gene therapy for ischemic heart disease.
Another approach we focused in this project is decoy oligonucleotides (ODN). Our in vivo study demonstrated that inhibition of transcription factor E2F or NFkB, which is considered to play important roles in mechanisms of restenosis after angioplasty. Now, clinical trials (Japan Trial to Prevent Restenosis After Angioplasty or Stentusing E2F decoy Oligodeoxynucleotides as Gene Therapy) (Japan Trial to Prevent Restenosis After Angioplasty or Stentusing NFkB decoy Oligodeoxynucleotides as Gene Therapy) are on going, suggesting the safety of ODN transfection.

10.Key Words
(1)HGF  (2)decoy oligonucleotides  (3)peripheral arterial disease 
(4)ischemic heart disease  (5)catheter  (6)restenosis 
(7)angiogenesis  (8)genomic medicine  (9)NFkB