April 25, 2008

Alliance seeks drug response factors

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Alfred George, M.D.

Alliance seeks drug response factors

Dan Roden, M.D.

Dan Roden, M.D.

Researchers at Vanderbilt Medical Center will participate in a new global effort to identify genetic factors that contribute to individual responses to medication, including rare and dangerous side effects.

A letter of intent to establish the Global Alliance for Pharmacogenomics, a collaboration of the National Institutes of Health (NIH) and the Center for Genomic Medicine, a component of the RIKEN Yokohama Institute in Japan, was announced last week.

“By bringing together our resources, we will advance the understanding of how changes in DNA affect our responses to medicines. Thus we can begin to realize the promise of personalized medicine,” Yusuke Nakamura, M.D., Ph.D., director of the RIKEN Center for Genomic Medicine, said in a news release.

Vanderbilt researchers will participate in two of the first five projects undertaken by the alliance.

Dan Roden, M.D., director of the Oates Institute for Experimental Therapeutics, and Alfred George, M.D., director of the Division of Genetic Medicine, will explore how genes contribute to drug-induced long QT syndrome, an irregular heart rhythm that can cause sudden cardiac arrest.

Roden and colleagues in the International Warfarin Consortium also will tailor initial doses of the common blood thinner warfarin based on patients' genetic profiles in an attempt to reduce the incidence of side effects from the drug, particularly severe bleeding.

“This is one area of science where bigger really is better,” said Roden, who also is assistant vice chancellor for Personalized Medicine.

Global networks allow researchers to identify a diverse range of relatively rare genetic variations associated with abnormal drug responses. Once those variations are identified, clinicians will be better able to “individualize” therapy to improve outcomes and minimize side effects.

“It's a win-win situation,” he said.

Vanderbilt is a leader in pharmacogenetics, the study of genetic factors that affect drug response.

About a dozen Vanderbilt researchers, led by Roden, are studying genetic predictors of arrhythmia, or abnormal heart rhythm, through the NIH-funded Pharmacogenetics Research Network.

Other alliance projects will examine genetic factors that influence the effectiveness of breast cancer treatments, and others that are linked to serious side effects from two drugs used to treat pancreatic cancer.