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Treatment of lupus in mice may point the way to human treatment

WINSTON-SALEM, N.C. Scientists at Wake Forest University Baptist Medical Center and the Medical University of South Carolina may be on the trail of a new treatment for systemic lupus, a disease that affects more than 1 million Americans, mostly women.

Nilamadhab Mishra, M.D., an instructor in internal medicine (rheumatology and clinical immunology), and his colleagues report in the Feb. 14 issue of the Journal of Clinical Investigation that they had found a drug that reduces symptoms of systemic lupus in mice.

The drug, called Trichostatin A or TSA, and other similar compounds "may have therapeutic benefit in treatment of systemic lupus erythematosus," the researchers said.

They said TSA leads to a significant reduction of excess protein in the urine, inflammation of the kidneys and spleen weight in the test mice when compared to control mice. Half of all untreated mice with systemic lupus die from kidney failure. Mice with lupus also develop massive spleens. "TSA-treated mice had significantly smaller spleens," Mishra and his colleagues said.

About half of human patients with systemic lupus have kidney problems, but achy joints, frequent fever, arthritis and prolonged or extreme fatigue are far more common symptoms. Some of these other symptoms also occur in the mice. Systemic lupus accounts for 70 percent of all lupus patients; the rest have one of three other varieties.

Lupus is known as an autoimmune disorder because the body's own immune system turns on the rest of the body and attacks tissue and organs including the joints, kidneys, heart, lungs, brain and blood. The immune system, which ordinarily protects the body from viruses, bacteria and other "foreign" invaders, loses the ability to tell the difference between foreign substances and its own cells and tissue.

The researchers also used TSA and another drug called SAHA (suberonylanilide hydroxamic acid) to study how systemic lupus occurs. Mishra said
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Contact: Robert Conn, Karen Richardson or Barbara Hahn
rconn@wfubmc.edu
336-716-4587
Wake Forest University Baptist Medical Center
15-Feb-2003


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