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| |  Discovery Provides Insight Into Causes of Asthma NUTLEY, N.J., May 13, 1995 -- One of nature's immune-system regulators, only recently discovered, could someday turn out to be a boon for people who suffer from respiratory disorders such as asthma, say researchers. Comparing normal mice with those genetically engineered to be incapable of making NFAT1 (Nuclear Factor of Activated T-cells-1), scientists were surprised to discover that the substance works in normal mice to moderate inflammation of the lungs during what, in people, would resemble an attack of asthma. "When exposed to an allergen that acts to sensitize the respiratory system, the body mounts an immune response," noted Steven Xanthoudakis, Ph.D., a central nervous system (CNS) researcher at Hoffmann-La Roche Inc. "In NFAT1-deficient mice, we see an inflammatory response that is more exaggerated than in normal mice." A similar hypersensitization to allergens is observed in people who suffer from asthma. "While this is of great interest, the research is still preliminary and without additional research; it will be difficult to determine how these findings in mice will relate to humans," he added. The findings -- stemming from a collaboration between Hoffmann-La Roche Inc., St. Jude Children's Research Hospital, Memphis, and Harvard Medical School (Dana Farber Cancer Institute), Boston -- were published in the May 10 issue of the journal Science. Dr. Xanthoudakis has co-headed the collaborative study of NFAT1 since its discovery by the Harvard group in 1993. "We expected to find that NFAT1 affects some feature or other of the immune response," he said. "What we didn't expect was that it moderates the very feature that causes people such severe discomfort when our bodies try to fight off allergens. If researchers could develop a drug to selectively and safely increase the body's production of NFAT1," he noted, "there are implications for developing new treatments for pulmonary disorders such as asthma." T-cells are sentinels of the immune system. When they detect foreign material in the blood, they send out messenger proteins (cytokines) that act to stimulate the immune system to fight off invasion by foreign substances. NFAT1 is one of several proteins that regulate transcription of information in the nucleus of the T-cell. Transcription is the process by which genetic DNA passes information to messenger RNA, which is then carried out of the nucleus to protein manufacturing sites in the cell. The proteins made there, and subsequently released into the blood stream, convey the information stored in T-cell genes. "Just how NFAT1 works to moderate inflammation remains a mystery," said Dr. Xanthoudakis. "We won't understand its role in this process until additional experiments can be conducted on the NFAT1-deficient mice." The research reported in Science will continue at Harvard under Anjana Rao, Ph.D., in collaboration with a team headed by Thomas Curran, Ph.D., at St. Jude. At Roche, scientists will continue exploring other aspects of NFAT function in search of new drugs to regulate the immune system. Both Drs. Xanthoudakis and Curran were associated with the Roche Institute of Molecular Biology before plans were announced to move it from Nutley to Palo Alto, Calif., last year. Dr. Xanthoudakis, a native of Montreal, Quebec, completed undergraduate work at that city's Concordia University in 1984. Upon earning a doctorate at Montreal's McGill University in 1990, he came to the Roche Institute to do post-doctoral research, and later joined the company's Department of CNS Research as a member of the Neurogenetics Group. He is the son of Mr. and Mrs. Theodore Xanthoudakis, of Montreal. ABOUT HOFFMANN-LA ROCHE INC. Headquartered in Nutley, N.J., Hoffmann-La Roche Inc. is an affiliate of the multinational group of companies headed by Roche Holding Ltd. of Basel, Switzerland. One of the world's leading research-intensive health care companies, Roche has discovered, developed and introduced numerous important prescription pharmaceuticals. The company is also a major provider of diagnostic products and services as well as vitamins, premixes and other products for human and animal nutrition and health. Recognized for excellence in both biotechnology and chemistry, Roche is also widely known for its current efforts in the research, development and commercialization of polymerase chain reaction (PCR) technology, a revolutionary advance in diagnostics and other fields, including biomedical research, forensics and environmental testing.
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