Gene Therapy against the Progressive Joint Destruction of Rheumatoid Arthritis and Osteoarthritis

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Rheumatoid Arthritis(RA) is a chronic inflammatory disease with the progressive joint distraction, from which more than eight hundred thousands people are suffered in our country. Osteoarthritis(OA) is also one of the most common general disease, and the more effective therapy should be needed when the number of the elderly people will increase in the near future. So we focused on NFκB to modulate the inflammatory cytokines or proteinase which are involved in the pathogenesis of RA and OA. We have already reported that NFκB plays an important role in a regulation of arthritis and decoy deoxynucleotide(ODN) can suppress the activation of NFκB by our original gene delivery system with HVJ-lipoisome. In This investigation, we prepared the experimental animal model of RA and OA to evaluate the efficacy of NFκB decoy ODN against the joint destruction of these arthritis. We showed NFκB decoy ODN suppressed the deterioration of collagen-induced arthritis(CIA) in rats via down-regulation of IL-Iβ and TNFα, and also confirmed the same results with CIA in monkeys. As the OA model, we established the rats with anterior cruciate ligament transection(ACLT). NFκB decoy ODN was also effective to the experimental arthritis. We concluded That the decoy strategy against NFκB is an effective therapeutic candidate for RA and OA. The clinical application of NFκB decoy ODN to the joints of RA patients will be following after these our results.