Osteoarthritis (OA) is a major health problem in urgent need of better treatment. Gene therapy offers to meet this need. Of the different strategies for using gene therapy in OA, local gene transfer to synovium is in the most advanced stage of development. Local gene transfer brings several advantages, including a focused, local therapy that promises greater efficacy with reduced side-effects, potentially at far lower cost. Moreover, its clinical feasibility has already been confirmed in two Phase I studies of gene therapy for rheumatoid arthritis. Although there are numerous candidate genes of potential use in treating OA genetically, considerable evidence identifies interleukin-1 (IL-1) as a key target. The existence of a natural antagonist, the IL-1 receptor antagonist (IL-1Ra), provides a means with which to inhibit its biologic actions. Clinical studies are suggested in which IL-1Ra complementary DNA is transferred to knee joints shortly before they are surgically replaced with prostheses. This will permit the ready assessment of the safety and efficiency of gene transfer and expression in the human OA knee, as well as permitting preliminary functional data to be obtained, as a prelude to phase II efficacy studies. At this point, the major barriers to progress are financial rather than intellectual or technical.
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