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Wednesday, September 9, 1998, 12:00 p.m. EDT
Scientists at NIEHS have identified a protein which may help in the quest for drugs to fight inflammatory diseases including rheumatoid arthritis, Crohn's disease, physical wasting, and graft-versus-host disease. The protein may help counteract the ill effects when the body produces excessive amounts of another protein key to fighting infection.
In proper balance, a bodily protein called tumor necrosis factor alpha performs like a hero, helping to fight infections and other bodily invaders. But like a hero gone awry, excessive TNF production stimulated by TNF itself can cause a host of inflammatory ills, such as those mentioned above, and the physical wasting that accompanies many cancers and AIDS.
Now, however, scientists at the National Institute of Environmental Health Sciences have identified a protein that can put the brakes on TNF.
Using genetically modified mice with a specific gene removed, researchers at the National Institute of Environmental Health Sciences have identified a protein that counters TNF, that in turn may lead to drugs that will curb TNF's ravages. This protein is called Tristetraprolin, or TTP.
In previous experiments, the researchers found that mice genetically modified to remove the TTP gene suffer many ailments similar to those associated with overproduction of TNF in people; yet when TNF is controlled in the mice, most of the TNF-induced problems do not develop. In their new study, published in Science (Vol. 281, p. 1001), the researchers found that this overproduction of TNF in the TTP deficient mice was due to the absence of TTP's controlling effect on TNF's synthesis by inflammatory cells.
Authors of the study are Ester Carballo, M.D., Ph.D., and Wi S. Lai, Ph.D., both of the Laboratory of Signal Transduction, NIEHS, and Perry J. Blackshear, M.D., D.Phil., Director of Clinical Research, NIEHS.
Dr. Blackshear said that TTP appears to regulate production of TNF by binding to and destabilizing the RNA that encodes TNF. Thus, he added, the benefits of TTP might be developed as a drug that mimics TTP action or that stimulates TTP production, or as gene therapy to increase TTP production in a patient.
The Food and Drug Administration recently approved a Crohn's disease drug, infliximab, that neutralizes TNF through another mechanism-but illustrating, Dr. Blackshear said, the applicability of the research in humans.
"We're exploring a partnership with a pharmaceutical company to develop drugs based on our discovery of TTP's role in regulating TNF," Dr. Blackshear said. "This new understanding of TTP's function could improve our ability to treat patients with a number of serious diseases, so we want to put this knowledge to work."
About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on NIEHS or environmental health topics, visit www.niehs.nih.gov or subscribe to a news list.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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