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Penn receives $12 million NIH grant to research personalized approach to smoking cessation
Date:9/7/2010

PHILADELPHIA A variety of smoking cessation treatments are currently available for the more than 18 million adult Americans try to quit smoking each year, but success rates vary widely. Despite the importance of quitting smoking, more personalized approaches to smoking cessation treatment are needed to help smokers pick the right method that will work best for them. A major new personalized medicine clinical trial, led by addiction researchers at the University of Pennsylvania, will study how a smokers' genetic make-up influences their quitting success.

A team of researchers led by Caryn Lerman, PhD, professor of Psychiatry at the University of Pennsylvania School of Medicine and Annenberg Public Policy Center, has received a $12 million five-year grant to study the pharmacogenetics of nicotine addiction treatment.

"In an extension of our previous work in the Pharmacogenetics of Nicotine Addiction Treatment (PNAT) research program, we will conduct the first large prospective pharmacogenetic clinical trial of different smoking cessation medications," said Dr. Lerman, who also serves as scientific director of Penn's Abramson Cancer Center. "Smoking is the greatest preventable cause of morbidity and mortality. It is imperative to find better ways to optimize the delivery of specific treatments to increase the success rates for smokers who wish to quit."

Earlier research by the PNAT research program identified a genetically-informed biomarker that reflects individual differences in the rate of nicotine metabolism how quickly nicotine breaks down in the body. This biomarker, referred to as the nicotine metabolite ratio (NMR), reflects genetic variation in the CYP2A6 gene, as well as environmental influences on nicotine metabolism.

Work by Dr. Lerman, Robert Schnoll, PhD, associate professor of Psychiatry at Penn, and PNAT collaborators has shown that the NMR can be used to predict the success of different smoking treatments for individual smokers. The new clinical trial will provide the next definitive step in their efforts to translate the use of this biomarker to clinical practice.

In this study, 1350 adult smokers will have their NMR assessed to determine whether they metabolize nicotine slowly or quickly. They will then be sorted into two groups slow metabolizers and normal metabolizers and randomized to treatment with a placebo, a nicotine patch, or Pfizer's Chantix (varenicline). Each participant will also provide genetic material (DNA) which will be used to identify additional gene variants that may also contribute to nicotine addiction treatment response. The prospective, double-blind placebo-controlled trial will be completed within the next four years.

The cost-effectiveness of the personalized medicine approach will be analyzed by Daniel Polsky, PhD, and Henry Glick, PhD, both from Penn's Leonard Davis Institute of Health Economics, and Daniel Heitjan, PhD, professor of Biostatistics and Statistics at Penn. Demonstrating that by matching smokers to treatment based on the NMR can increase quit rates and be achieved at a reasonable financial cost will support efforts to translate these pharmacogenetic approaches into clinical practice.

The trial is co-led by Dr. Rachel Tyndale at the University of Toronto and includes the University of California, San Francisco, MD Anderson Cancer Center, SRI International, University of Southern California, and the State University of New York at Buffalo. The grant is supported by the National Institute on Drug Abuse, the National Cancer Institute, the National Institute of General Medical Sciences, and the National Human Genome Research Institute as part of the Pharmacogenetics Research Network (PGRN) Initiative.


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Contact: Kim Guenther
kim.guenther@uphs.upenn.edu
215-662-6183
University of Pennsylvania School of Medicine
Source:Eurekalert

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