Gene therapy of rheumatoid arthritis by means of cytokine modulation

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Project objective

Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease of unknown etiology. This project will investigate a gene therapeutic approach of trerating RA in animal models of arthritis, using novel cytokine modulating techniques. The proinflammatory cytokine tumor necrosis factor a (TNFa) has been clearly demonstrated to be of pivotal importance in RA. Animal studies and clinical trials agree that treatment with a monoclonal anti-TNFa antibody produces a dramatic clinical remission and a striking response in acute phase reactants. The anti-inflammatory cytokine IL-10 has also been demonstrated to have a dose-dependent ameliorating effect on murine collagen arthritis, acting partly via TNFa inhibition. The major problem with biological treatment of RA is that therapy needs to be delivered continuously during a long time. One way of achieving prolonged and continuous delivery of TNFa inhibitors or IL-10 would be to use gene therapy. The objectives are: 1. To assess the use of adenoviral vectors to transfer cytokine inhibitory molecules in vitro and in the murine collagen arthritis model, 2. To compare the efficacy of gene therapy with that of biological therapy with IL-10 or anti-TNFa antibodies, and 3. To compare intravenous and local (intra-articular) gene transfer by viral vectors in this murine model. If these gene therapeutic cytokine modulation strategies are safe and at least as effective as treatment with anti-TNFa antibodies or IL-10, clinical trials of cytokine modulating gene therapy in patients with early RA will be possible. The Kennedy Institute is a leading research laboratory and has excellent resources for doing the work proposed. They also have much experience with the murine collagen arthritis model, needed to assess in vivo results. A group is already working with the problem of gene therapy in this murine model. The experience of working with gene therapeutic techniques in animal models of arthritis within this group will vastly extend my capacity as a researcher and be of great value to me for my future work in experimental rheumatology.

Original text from CORDIS.

Participants

• THE MATHILDA AND TERENCE KENNEDY INSTITUTE OF RHEUMATOLOGY · LondonCoordinatorUnited Kingdom
• Not availableCity levelSweden

Links

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