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DEVELOPMENT OF A NOVEL GENE THERAPY FOR RHEUMATOID ARTHRITIS UTILIZING EC-SOD GENE

Research Project

Project/Area Number 12671430
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionSAPPORO MEDICAL UNVERSITY

Principal Investigator

KOGAWA Katsuhisa  SAPPORO MEDICAL UNVERSITY School of medicine, assistant professor., 医学部, 講師 (60244349)

Co-Investigator(Kenkyū-buntansha) YAMASHITA Toshihiko  SAPPORO MEDICAL UNVERSITY School of medicine, associate professor, 医学部, 助教授 (70244366)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsEC-SOD / Rheumatoid Arthritis / Gene Therapy / Fibroblast / 繊維芽細胞
Research Abstract

Superoxide dismutase (SOD) is a potent anti-inflammatory enzyme that has therapeutic potential. We examined the efficiency of extracellular superoxide dismutase (EC-SOD) gene therapy on murine collagen-induced arthritis (CIA). Embryonic DBA/1 fibroblasts were infected with a retrovirus expressing human EC-SOD. DBA/1 mice immunized with collagen II were treated with subcutaneous inoculation of 2xl07 ECSOD expressing fibroblasts. The severity of arthritis in mice was evaluated botn clinically and histologically. Then, high levels of serum EC-SOD concentration were attained in mice at least for 7days. The transgene was shown to provide a significant suppression of disabling joint swelling, deformity and hind paw thickness, as compared to that found in the untreated groups. Histological abnormalities including destruction of cartilage and bone, infiltration of mononuclear cells and proliferation of synovial cells in the EC-SOD treated mice were also markedly improved compared to those of the control group. These results indicate that EC-SOD gene transfer may serve as an effective form of therapy for rheumatoid arthritis (RA).

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Iyama, S., Kogawa, K., et al.: "Treatment of Collagen-induced Murine Arthritis by Ex-Vivo EC-SOD Gene Transfer"Arthritis Rheum.. 26. 2160-2167 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iyama, S., et al.: "Gene therapy with extracellular superoxide dismutase ameliorates experimental colitis in mice.Molecular Therapy"Molecular Therapy. 1. S303 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka, M., et al.: "Anti-metastatic gene therapy utilizing subcutaneous inoculation of EC-SOD gene transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and LL cells in mice"Gene Ther.. 8. 149-156 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iyama, S., Okamoto, T., Sato, T., Yamauchi, N., Sato, Y., Sasaki, K., Takahashi, M., Tanaka, M., Adachi, T., Kogawa, K., Kato, J., Sakamaki, S., and Niitsu, Y: "Treatment of murine collagen-induced arthritis by ex viyo extracellular superoxide dismutase gene transfer."Arthritis Rheum.. 44(9). 2160-2167 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iyama, S., Takahashi, M., Sato, T., Okamoto, T., Yoshizaki, N., Sakamaki, S., and Niitsu, Y.: "Gene therapy with extracellular superoxide dismutase ameliorates experimental colitis in mice."Molecular Therapy. 1(5). S303 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka, M., Kogawa, K., Nakamura, K., Nishihori, Y, Kuribayashi, K., Hagiwara, S., Muramatsu, H., Sakamaki, S., and Niitsu, Y.: "Anti-metastatic gene therapy utilizing subcutaneous inoculation of EG-SOD gene transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and 3LL cells in mice."Gene Ther. 8(2). 149-156 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kogawa, K., Muramatsu, H., Tanaka, M., Nishihori, Y, Hagiwara, S., Kuribayashi, K., Nakamura, K., Koike, K., Sakamaki, S., and Niitsu, Y: "Enhanced inhibition of experimental metastasis by the combination chemotherapy of Cu-Zn SOD and adriamycin."Clin Exp Metastasis.. 17(3). 239-244 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka, M., Kogawa, K., Nishihori, Y, Kuribayashi, K., Nakamura, K., Muramatsu, H., Koike, K., Sakamaki, S., and Niitsu, Y: "Suppression of intracellular Cu-Zn SOD results in enhanced motility and metastasis of Meth A sarcoma cells"Int J Cancer. 73(2). 187-92 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Muramatsu, H., Kogawa, K., Tanaka, M., Okumura, K., Nishihori, Y., Koike, K., Kuga, T., and Niitsu, Y: "Superoxide dismutase in SAS human tongue carcinoma cell line is a factor defining invasiveness and cell motility"Cancer Res. 55(24). 6210-4 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iyama, S., Kogawa, K., et al.: "Treatment of Collagen-induced Murine Arthritis by Ex-Vivo EC-SOD Gene Transfer"Arthritis Rheum.. 26. 2160-2167 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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