In people with rheumatoid arthritis, the joint cells produce three to five times as much IL-1ra as they produce of the inflammatory protein, but for the treatment to be effective researchers believe they would need to widen the ratio to 50-to-1 or even greater, said Christopher Evans, a Harvard School of Medicine professor of orthopedic surgery who also was involved in the study.

In order for inhibition to occur there needs to be a very large excess of IL-1ra, Evans said.

The team used about 250 male rats, genetically modified to have no immune systems. Three groups of rats were used - a control group that received no gene therapy, and two groups that received the modified gene, each delivered through a different virus carrier.

Researchers injected the carrier into the capsule of each rat ™s rear knee joint. IL-1ra production was highest during the first week, but declined for about six weeks until it stabilized at 25 percent to 30 percent of the initial level and remained at that level for the lifetimes of the animals.

We had exactly the same profile of expression (in both gene therapy groups), which meant that joint tissues were capable of expressing a therapeutic gene indefinitely, and that the type of virus used for gene delivery did not make a difference, Gouze said.

Development of gene therapy treatments for pathologies associated with arthritis using IL-1ra could be one aspect of a huge boom in biotech treatments for orthopedic conditions, said Paul D. Robbins, a professor of molecular genetics and biochemistry at the University of Pittsburgh. Robbins performed pioneering IL-1ra gene therapy studies in the early 1990s. Ghivizzani was a researcher in Robbins ™ laboratory before going on to Harvard but did not collaborate with him on the current study.

I think orthopedics is going to be one of the areas where gene therapy is going to be very successful, Robbins said, because you ™re taking a natural healing process that may be slow or not as effective for whatever reason and making it better by gene transfer. napa.ufl