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2001 Fiscal Year Final Research Report Summary

Application of In vivo Gene Transfer for the Analysis of Pathophysiology and Treatment in the Cardiovascular Disease

Research Project

Project/Area Number 11470163
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionOsaka University

Principal Investigator

MORISHITA Ryuichi  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40291439)

Co-Investigator(Kenkyū-buntansha) KANEDA Yasufumi  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (10177537)
HIGAKI Jitsuo  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70189744)
Project Period (FY) 1999 – 2001
Keywordsgene therapy / angiogenesis / ASO / HGF / CAP / endotlelial cells / ASO
Research Abstract

Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as peripheral arterial disease, restenosis after angioplasty, vascular bypass graft occlusion, transplant coronary vasculopathy, myocardial infarction, for which no known effective therapy exists. Recently, the efficacy of therapeutic angiogenesis using VEGF (vascular endothelial growth factor) gene transfer has been reported in human patients with critical limb ischemia and myocardial ischemia. Thus, the strategy for therapeutic angiogenesis using angipgenic growth factors should be considered for the treatment of patients with critical limb ischemia or myocardial infarction. From this viewpoint, we focused on a novel angiogenic growth factor, HGF (hepatocyte growth factor). Although HGF is originally identified as a most potent mitogen for hepatocytes, we found the potent angiogenic property of HGF in rabbit hindlimb model. Accordingly, we planed human clinical trial using intramuscularl … More y injection of naked human HGF plasmid (0.5mg x 4) two times. Currently, HGF gene transfer was performed in 6 patients with PAD (n=3) or Buerger (n=3) graded by Fontaine III or IV who had failed conventional therapy. Reduction of pain scale (>1cm in visual analog scale) was observed in 5 of 6 patients (efficacy rate is 83%). Increase in ABI (Ankle Pressure Index) >0.1 was observed in 5 of 5 patients (efficacy rate is 100%), while 1 patients failed to measure API from before gene therapy due to strong calcification. In addition, TPI (Toe pressure Index) was also Increased in 2 of 2 patients (efficacy rate is 100%), whereas other 3 patients failed to measure TPI from before gene therapy due to ischemic ulcer. Currently, severe adverse effects could not be detected in all patients. Although the present data are still preliminary, the initial clinical outcome with naked HGF plasmid DNA transfer seems to be useful as sole therapy for PAD. In addition, we proved the potent angiogenic activity of HGF in the stimulation of collateral formation in myocardium. Based upon these findings, we submitted human clinical trial using HGF to treat chronic heart failure. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angioge nesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: preclinical study for treatment of peripheral arterial disease"Gene Therapy. 8. 181-189 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi K, Morishita R, Nakagami H, Yoshimura S, Hara A, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T, Sakai N: "Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neurons"Gene Therapy. 8. 1167-1173 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniyama Y, Morishita R, Hiraoka K, Aoki M, Nakagami H, Yamasaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model: molecular mechanisms of delayed angiogenesis in diabetes"Circulation. 104. 2344-2350 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshimura S, Morishita R, Hayashi K, Yamamoto K, Nakagami H, Kaneda Y, Sakai N, Ogihara T: "Inhibition of intimal hyperplasia after balloon injury in rat carotid artery model using cis-element 'decoy' of nuclear factor-kB binding site as a novel molecular strategy"Gene Therapy. 8. 1635-1642 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniyama Y, Tachibana K, Hiraoka K, Namba T, Yamasaki K, Hashiya N, Aoki M, Ogihara T, Yasufumi K, Morishita R: "Local delivery of plasmid DNA into rat carotid artery using ultrasound"Circulation. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura T, Morishita R, Asai T, Tsuboniwa N, Aoki M, Sakonjo H, Yamasaki K, Hashiya N, Kaneda Y, Ogihara T: "Molecular strategy using cis-element 'decoy' of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model"Gene Therapy. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morishita R, Aoki M, Hashiya N, Yamasaki K, Makino H, Wakayama K, Azuma J, Ogihara T: Gene Therapy & Regulation. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniyama Y, Morishita R, Aoki M, Nakagami H, Yamamoto K, Yamazaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hind limb ischemia module: preclintcal study of treatment of peripheral arterial disease"Gene Therapy. (8). 181-189 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi K, Morishita R, Nakagami H, Yoshimura S, Hara A, Matsumoto K, Nakamura T, Kaneda Y, Sakai N: "Gene therapy for preventing neuronal death using hepatocyte growth factor in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CAI neurons"Gene Therapy. (8). 1167-1173 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniyama Y, Morishita R, Hiraoka K, Aoki M, Nakagami H, Yamasaki K, Matsumoto K, Nakamura T, Kaneda Y, Ogihara T: "Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischernia module: molecular of delayed angiogenesis in diabetes"Circulation. (104). 2344-2350 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimura Y, Morishita R, Hayashi K, Yamamoto K, Nakagami H, Kaneda Y, Sakai N, Ogihara T: "Inhibition of intimal hyperplasic after balloon injury in rat carotid artery model using cis-elememt "decoy" of nuclear factor-kB binding afte a novel molecular strategy"Gene therapy. (8). 1635-1642 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniyama Y, Tachibana K, Hiraoka K, Namba T, Yamasaki K, Hashiya N, Aoki M, Ogihara T, Kaneda Y, Morishita R: "Local delivery of plasmid DNA into rat carotid artery using ultrasound"Circulation. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura T, Morishita R, Asai T, Tsuboniwa N, Aoki M, Sakonjo H, Yamasaki K, Hashiya N, Kaneda Y, Ogihara T: "Molecular strategy using cis-element "decoy" of E2F binding alto inhibits neointimal formation in porcine balloon-injured coronary asiesy model."Gene Therapy. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morishita R, Aoki M, Hashiya N, Yamasaki K, Makino H, Wakayama K, Azuma J, Ogihara T: Gene Therapy & Regulation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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