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Synthetic protein eases arthritis symptoms in mice

A lab-made version of a human protein alleviates symptoms of both acute and chronic arthritis in mice and could be the basis for a new arthritis drug for people, report scientists from the National Institute of Allergy and Infectious Disease (NIAID), part of the National Institutes of Health (NIH). The protein prevents the assembly of a cell surface receptor, thus blocking transmission of chemical signals that lead to arthritis symptoms.

"This study opens a new research avenue to better understand and, perhaps, to treat rheumatoid arthritis, a condition that causes suffering in more than two million Americans," says NIAID Director Anthony S. Fauci, M.D.

Investigators from NIAID's Laboratory of Immunology, led by Michael Lenardo, M.D., published their findings in the October issue of Nature Medicine, now available online. The idea that the protein, called pre-ligand assembly domain protein or PLAD, might play a role in thwarting the joint inflammation characteristic of rheumatoid arthritis--one of the most common autoimmune diseases--grew out of their research on a very rare autoimmune disease called autoimmune lymphoproliferative syndrome (ALPS).

Previously, Dr. Lenardo and his colleagues showed that in ALPS a form of PLAD blocks a cell surface receptor and prevents a needed chemical signaling pathway from functioning correctly. In ALPS, the signal pathway interrupted by PLAD leads to disease symptoms. But, the scientists reasoned, PLAD might also be able to block a related cell surface receptor--one involved in passing signals that lead to inflammation. In theory, inhibiting this pathway might benefit people with rheumatoid arthritis, who suffer from excessive inflammation.

A key promoter of inflammation is a chemical called tumor necrosis factor alpha (TNF-alpha). TNF-alpha starts a chemical chain reaction leading to inflammation by binding to two cell surface receptors, TNFR-1 and TNFR-2. Naturally occurring PLAD helps both forms
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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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