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Week of 30 April 1999 Vol. II, No. 33 Feature Article New promise for controlling lupus and diabetes BU scientists discover gene involved in inflammatory diseases Boston University scientists recently discovered a gene involved in inflammatory diseases such as rheumatoid arthritis and Crohn's disease. The discovery, published April 13 in the Proceedings of the National Academy of Sciences, was made by a team led by Dr. Salomon Amar, associate professor of oral biology and periodontology at the Boston University School of Dental Medicine. The report details how the researchers found a gene that encodes for the molecule believed to be involved in a variety of inflammatory diseases, including periodontal disease, septic shock, lupus, and diabetes. "We believe this discovery offers new insights into how the body regulates the fundamental pathway involved in inflammation and opens up new ways to find and to treat currently untreatable diseases," says Amar. Dr. Salomon Amar The scientists identified the gene that controls production of Tumor Necrosis Factor alpha (or TNF), a molecule the body produces when it needs to destroy unwanted tissues -- when it is fighting infection, for example. The body tightly regulates molecules such as TNF that exert powerful effects, facilitated through proteins called transcription factors. The researchers believe that this molecule is implicated in a wide variety of inflammatory diseases -- diseases in which the body literally attacks itself. The BU scientists deleted portions of the promoter of the TNF gene and tested whether or not the gene continued to function. They found that if a particular sequence were removed, cells could not produce TNF. They also found that this sequence binds a previously unknown transcription factor. They named this molecule LITAF (lipopolysaccharide-induced transcription factor). These findings, according to the report, "suggest that LITAF plays an important role in the activation of the human TNF gene and propose a new mechanism to control TNF gene expression." At present, two pharmaceutical companies are developing anti-TNF therapies for Crohn's disease. However, both protein molecules under development are too expensive and difficult to administer to be ideal for the long-term therapy necessary for such chronic conditions. The Boston University discovery will use LITAF to produce small molecule therapeutics that can be used more easily and economically to treat diseases such as Crohn's, which causes inflammation of the small intestine. Treatment can help control Crohn's disease, but there is no known cure. The other scientists on the team are Fumio Myokai and Shogo Takashiba, researchers at the BU School of Dental Medicine, and Roger Lebo, associate professor at the BU School of Medicine's Center for Human Genetics. The research leading to this discovery was supported by the National Institute of Craniofacial and Dental Research of the National Institutes of Health.