2001 Fiscal Year Final Research Report Summary
DEVELOPMENT OF A NOVEL GENE THERAPY FOR RHEUMATOID ARTHRITIS UTILIZING EC-SOD GENE
| Project/Area Number |
12671430
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | SAPPORO MEDICAL UNVERSITY |
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Principal Investigator |
KOGAWA Katsuhisa SAPPORO MEDICAL UNVERSITY School of medicine, assistant professor., 医学部, 講師 (60244349)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Toshihiko SAPPORO MEDICAL UNVERSITY School of medicine, associate professor, 医学部, 助教授 (70244366)
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| Project Period (FY) |
2000 – 2001
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| Keywords | EC-SOD / Rheumatoid Arthritis / Gene Therapy / Fibroblast |
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| 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).
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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[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)
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[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)
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