First Evidence That Localized Arthritis Gene Therapy Heals Distant Diseased Joints

Local production of the modified TNF" and IL-1 receptors would be expected to "mop up" extra TNF" and IL-1 before they could bind to receptors on synoviocytes.

The researchers induced arthritis in both knees of 32 rabbits. One day later, some rabbits received the gene for the receptor to TNF" in one diseased knee. (The second knee served as a control). Other rabbits received the gene for the receptor to IL-1 in one diseased knee. A third group of rabbits received genes for both IL-1 receptor and TNF" receptor in one diseased knee. A fourth group of rabbits received a control injection of saline solution or an irrelevant gene in one diseased knee.

The IL-1 receptor gene or the IL-1 receptor gene given together with the TNF" receptor gene lessened inflammation and cartilage destruction in the rabbit joints. To detect these effects, the researchers collected joint fluid and found reductions in the number of white blood cells (indicative of inflammation) and the amount of proteins normally associated with cartilage destruction. Unexpectedly, the investigators found that the altered IL-1 receptor gene, alone or together with altered TNF" receptor gene diminished arthritic effects in untreated, distant knee joints.

"The best therapeutic effect appears when the IL-1 receptor gene and the TNF" receptor gene are combined," noted Dr. Ghivizzani. "Knees injected with both these genes showed an 85-90 percent reduction in white blood cell levels compared with untreated knees, and a similar protection of cartilage."

In a related experiment, the investigators injected an adenovirus containing a marker gene into one knee of several rabbits. Although not therapeutic, a marker gene allows scientists to easily track the distribution of introduced genes within the body. Seven days after injecting the marker gene, the researchers analyzed tissues and fluids from both rabbit knee joints. They found the marker gene had been

Contact: Lauren Ward
University of Pittsburgh Medical Center

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