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Synthetic protein eases arthritis symptoms in mice

of TNFR assemble and prepare to receive TNF-alpha. Synthetic PLAD, the scientists hypothesized, would bind to its natural counterpart and prevent it from performing its usual task.

The scientists used a variety of techniques (including injection of TNF-alpha) to induce arthritis symptoms in mice. Researchers also injected some of the animals with lab-made PLAD (P60 PLAD). "We found that P60 PLAD protein powerfully inhibited the symptoms of TNF-alpha-induced arthritis," says Dr. Lenardo. P60 PLAD also lessened the effects of arthritis induced by other means. Moreover, he adds, P60 PLAD appeared to inhibit disease symptoms in mice with established as well as acute arthritis. The scientists did not detect any obvious toxicity in the PLAD-treated mice.

"We're very hopeful that this could be good news for arthritis sufferers," says Dr. Lenardo. In particular, the researchers are intrigued by P60 PLAD's apparent specificity: it seems to block the binding of TNF-alpha to TNFR-1, while allowing TNFR-2 to continue to function. This is important, notes Dr. Lenardo, because it may represent an advantage over some currently used arthritis drugs, which directly block TNF-alpha by binding to both TNFRs and thereby inhibit beneficial actions mediated by TNFR-2.

The scientists next aim to develop a more stable form of P60 PLAD. Ultimately, they hope to test the protein in clinical trials.


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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
3-Oct-2005


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