New compound holds promise for lupus and related diseases

Ann Arbor, MI A chemical cousin of anti-anxiety medications, such as Valium and Xanax, significantly reduces kidney inflammation in mice inbred to develop a disease resembling human systemic lupus erythematosus (SLE), researchers at the University of Michigan and the University of California-Berkeley have found.

Their research, described in the Oct. 16 issue of the Journal of Clinical Investigation, also reveals the novel mechanism by which the compound works, a discovery that could lead to safer and more effective new drugs for managing lupus and other autoimmune disorders.

"The best available therapies for lupus haven't changed for many, many years," says U-M's Gary D. Glick, Ph.D., one of the lead authors on the study. "It's a disease where the mechanisms that normally prevent the immune system from attacking components of one's own body are defective. Because we do not yet understand what triggers lupus, it has been very difficult to develop lupus-specific therapies."

In fact, the mainstays of treating lupus-related kidney inflammation---the major cause of illness and death in lupus patients---are drugs developed many years ago to kill cancer cells. When given to lupus patients, often in combination with immune-suppressing steroids, these cytotoxic agents kill immune cells. But because they lack specificity, they also kill healthy cells, resulting in serious side effects. What's more, they simply are not effective in some patients.

"Our compound, on the other hand, goes in and kills the bad players but leaves the good players alone," says Glick, a charter faculty member of the U-M Life Sciences Institute, who is the Werner E. Bachmann Collegiate Professor of Chemistry, and a professor of biological chemistry in the U-M Medical School.

The compound, a 1,4-benzodiazepine (designated as Bz-423), sets off a chain of events that results in apoptosis, a natural cell-suicide process by which the body rids itself of cells

Contact: Sally Pobojewski
University of Michigan Health System

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