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

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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).