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International functional genomics study looks for genes that cause drug tolerance and dependence

Researchers at Doernbecher Children's Hospital are part of a new study they hope will identify genes that contribute to drug tolerance and dependence. For patients with chronic pain, this could put an end to high doses of various medications and the adverse side effects of tolerance. Instead, more effective versions of drugs, such as those that mimic morphine, may be developed that allow patients to take pain medications for longer periods of time without becoming physically dependent on them.

"In general life, tolerance and dependence are day-to-day issues, such as the use of alcohol or caffeine. What this grant will help us to understand is how we develop that tolerance so we can use the mechanisms to create better therapeutics and also to develop better preventive measures for dependence," said Srinivasa R. Nagalla, M.D., principal investigator for the OHSU component of this study and director of Doernbecher's Center for Biomarker Discovery.

The four-year, $1.4 million study is funded by the National Institute on Drug Abuse (NIDA). Doernbecher's team was chosen for its genomics and proteomics expertise, and will determine the gene expression of regular mice versus genetically altered mice who do not become tolerant of, or dependent, on pain medication. The Robert Wood Johnson Medical School at the University of Medicine & Dentistry of New Jersey (UMDNJ) and the University of Louis Pasteur (U. Louis Pasteur) of France are the two other participating sites that have developed these mice models. This unique collaboration across international lines will allow each institution to offer its expertise to the study.

Genomics uses DNA chips to determine which genes are turned on and turned off, or normal versus abnormal, to determine which genes are expressed in a particular disease or condition. Proteomics takes that a step further to analyze the characteristics and activity of the proteins that are produced from those genes.

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Contact: Christine Pashley
pashleyc@ohsu.edu
503-494-1360
Oregon Health & Science University
19-Dec-2002


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