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First Evidence That Localized Arthritis Gene Therapy Heals Distant Diseased Joints

PITTSBURGH, April 13 -- University of Pittsburgh researchers have made the unprecedented and totally unexpected finding that localized gene therapy for arthritis produces healing effects on distant joints affected with the disease. Results of this landmark study, conducted in a rabbit model of rheumatoid arthritis, appear in the April 15 issue of the Proceedings of the National Academy of Sciences. It is a major advance in the quest to bring arthritis gene therapy into widespread clinical use.

"This offers the first evidence that arthritis gene therapy can produce widespread, or systemic, effects. Our hope is that it would be possible to inject one arthritic joint in a patient with a therapeutic gene and find that arthritic joints elsewhere in the body respond to this therapy," said Steve Ghivizzani, Ph.D., a post-doctoral fellow in the department of molecular genetics and biochemistry at the University of Pittsburgh and lead author of the study.

Rheumatoid arthritis (RA), which affects about 2.1 million Americans, causes painful inflammation and erosion of joints. This disease process has been linked with two proteins, interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF"), which are overproduced in arthritic joints. These substances bind to specific receptors located on cells lining joints (synoviocytes). In doing so, they trigger the progressive, irreversible destruction caused by RA. Researchers have long sought to block the action of these proteins to reduce or halt the disease process.

In their study, the Pitt investigators provoked rheumatoid-like arthritis in rabbit knee joints by injecting them with a protein that causes inflammation and joint erosion. The investigators used an adenovirus (a virus that causes the common cold) to carry therapeutic genes, in this case genes for an altered form of cell receptors for TNF" and IL-1. The adenovirus used was disabled to render it harmless.
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Contact: Lauren Ward
wardla@a1.isd.upmc.edu
412-624-2607
University of Pittsburgh Medical Center
14-Apr-1998


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