Organ-Transplant Agent May Work on Autoimmune Diseases

A compound related to a drug used in humans to prevent organ-transplant rejection has been found to attack a major biochemical process in the faulty immune cells of lupus-prone mice, suggesting a possible new approach to fighting the disease.

"We found that an analog of rapamycin is very effective in improving all aspects of the disease in lupus-prone mice,” said Dr. Chandra Mohan, professor of internal medicine at University of Texas-Southwestern Medical Center (Dallas, TX, USA) and senior author of a study appearing in the August 2007 issue of the Journal of Clinical Investigation. "Our next step will be to see if the same biochemical pathways exist in humans. If they do, this research and treatment could prove very significant.”

Lupus is a chronic autoimmune disease in which the immune system attacks the body's cells and tissues. In a healthy immune system foreign intruders are recognized by special immune cells called B-cells that produce antibodies. In patients with lupus, however, the antibodies created by the B-cells begin to attack the body itself.

Certain genetic strains of mice are prone to developing lupus. In the current study, a research team led by Dr. Mohan found that an analog of rapamycin inactivates specific biochemical processes in the B-cells of the mice. Rapamycin has been used in humans to prevent organ transplant rejection and for treating cancer. The analog of rapamycin blocked production of antibodies and the development of lupus in all the strains of lupus-prone mice, as well as improved symptoms, despite each animal having a different genetic composition that led to the disease.

"Though lupus in different mouse models may originate from different genetic triggers, those triggers ultimately funnel through a shared series of biochemical pathways that lead to the disease,” Dr. Mohan said. "These shared biochemical pathways represent an attractive target for future therapeutic intervention in lupus patients.”

In humans, lupus can cause life-threatening damage to the kidneys, lungs, heart, central nervous system, joints, blood vessels, and skin. It can be associated with severe fatigue, joint pain, skin rashes, hair loss, and neurologic problems. Although treatable symptomatically, there is currently no cure for the disease, which affects up to one million people in the United States alone.


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University of Texas-Southwestern Medical Center