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

超氧化物歧化酶是一种具有治疗潜力的强效抗炎酶。我们检测了细胞外超氧化物歧化酶(EC-SOD)基因治疗小鼠胶原性关节炎(CIA)的有效性。用表达人EC-SOD的逆转录病毒感染胚胎DBA/1成纤维细胞。用II型胶原免疫DBA/1小鼠，皮下接种2×10~7表达ECSOD的成纤维细胞。从临床和组织学角度评价BOTN对小鼠关节炎的影响。然后，小鼠的血清EC-SOD水平至少在7天内达到高水平。与未治疗组相比，转基因对致残性关节肿胀、畸形和后爪厚度有显著的抑制作用。EC-SOD治疗组小鼠关节软骨、骨质破坏、单个核细胞浸润和滑膜细胞增殖等组织学改变也明显改善。提示EC-SOD基因转移治疗类风湿性关节炎可能是一种有效的治疗方法。

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).