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New Drug May Ease Lupus Complication

Chemical cousin of Valium prevents kidney problems in mice

THURSDAY, Oct. 17, 2002 (HealthDayNews) -- A new compound, tested on lab animals with a disease similar to human lupus, helps reduce the kidney inflammation that's common among people with the ailment.

Researchers hope it will prove to be a promising new treatment for the baffling disease, in which the body turns on itself.

A chemical cousin of anti-anxiety medications such as Valium and Xanax, the new compound reduced the inflamed kidneys of mice bred to develop a condition similar to human systemic lupus erythematosus or SLE, researchers from the University of Michigan and the University of California at Berkeley report in the latest issue of the Journal of Clinical Investigation.

"It wouldn't be a cure [for lupus]," says Gary D. Glick, a professor of biological chemistry at the University of Michigan Medical School and one of the study's lead authors. "But we believe it could arrest the progression of kidney disease. Maybe 25 to 50 percent of lupus patients have kidney disease."

Before that becomes reality, he stresses, the compound must be tried in humans and gain government approval, a process that typically takes several years.

Up to 1.5 million Americans have been diagnosed with lupus, according to the Lupus Foundation of America. The chronic inflammatory disease can affect various parts of the body, including the joints, blood, kidneys, lungs and skin. It can be fatal. A lupus patient's immune system loses the ability to detect the difference between foreign substances it should be attacking and its own healthy cells and tissues.

Currently, doctors treat lupus-related kidney inflammation with immune-suppressing drugs to stabilize the overactive immune system, as well as cytotoxic agents. However, those agents kill off healthy cells as well as the cells they are aiming to kill, resulting in serious side effects.

The compound tested by the Michigan and California scientists, a benzodiazepine they term Bz-423, kills off only the "bad players," as Glick puts it. "It kills the lupus cells and spares the healthy immune cells," he says.

When they gave the compound to mice with lupus, 16 percent of them got lupus-related kidney disease. In the meantime, 60 percent of the untreated group of mice had kidney problems.

"What was really interesting was the effect of our drug was concentrated on a certain group of cells, the ones critical in mediating kidney disease," Glick says. "And it left the other immune cells alone."

Eventually, the new drug might negate the need for prednisone, a lupus drug that works by stabilizing the overactive immune system. It also may let patients take lower doses of prednisone, thus reducing its side effects, Glick says.

Another expert praises the study. "I think it's an important advance with a new compound that has the potential to alter the immune system so that it is less likely to be autoimmune," says Dr. Bevra Hahn, a professor of medicine and chief of rheumatology at the David Geffen School of Medicine at the University of California at Los Angeles.

"The fact that it's a benzodiazepine is a little confusing [to people] because a lot of people have experience taking benzodiazepines -- such as Valium, for instance. Although this [new compound] is chemically related, it does not have the same effects," Hahn explains. "This is a new idea on how to change the behavior of the immune system so it's less likely to turn against the body. It opens up a new approach."

What To Do

For more information on lupus, see the Lupus Foundation of America and the National Institutes of Health.

SOURCES: Gary D. Glick, Ph.D., professor, biological chemistry, University of Michigan Medical School, Ann Arbor; Bevra Hahn, M.D., professor, medicine, and chief, rheumatology, David Geffen School of Medicine, University of California, Los Angeles; Oct. 16, 2002, Journal of Clinical Investigation
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