|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|
|6.Title of Project||Development of New Therapeutics Using Angiogenesis and Regeneration of Endothelial Cells|
|Name||Institution,Department||Title of Position|
|Ryuichi, Morishita||Osaka University, Graduate School of Medicine||Professor|
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.