Ohio State University receives five-year grant to improve drug therapy using gene profiles

The National Institute of General Medical Sciences has awarded a $9.1 million, five-year grant to The Ohio State University for a study titled "Expression Genetics in Drug Therapy." The goal of the research is to enhance drug response rates and reduce the number of adverse drug reactions among patients taking medication.

The grant also funds Ohio State as a member of a nationwide Pharmacogenomics Research Network (PGRN), which connects 14 major centers across the United States with diverse specializations, working jointly to achieve this goal.

"It's estimated that 30 percent to 70 percent of people who take medication do not respond favorably and even have serious adverse reactions to it," says study leader Wolfgang Sadee, chair and professor of pharmacology, of pharmacy, of internal medicine, of psychiatry and of public health at The Ohio State University. Sadee also chairs Ohio State's Program in Pharmacogenomics.

Sadee notes that adverse drug reactions are a major cause of death and hospitalization in the United States. "We want to improve our ability to give the right drug to the right patient at the right time at the right dosage," adds Sadee.

"Because people are genetically different, they respond differently to medication," he says. "If we can identify these genetic differences, then we can prevent adverse drug reactions and predict which drugs will offer the best treatment for individual patients."

But critical genetic differences among individuals largely remain unknown, Sadee says. "Our project uses a novel approach to finding these critical genetic differences and testing them immediately in clinical trials that are under way here at Ohio State and across the world." The project will also support large-scale DNA sequencing using the latest technologies, enabling researchers to study the entire human genome.

The study led by Sadee targets genes that are important for major diseases such as central nervous system disorders, cardiovascular disease, cancer, and their therapies. It further includes new projects driven by a clinical need, such as nephritic syndrome in children to understand why some children do not respond to standard therapy.

The project involves collaborations with researchers at The Ohio State University Dorothy Davis Heart and Lung Research Institute, Ohio State's Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Nationwide Children's Hospital in Columbus, and at medical centers in the US, Canada, and Europe.

Ohio State's pharmacogenomics program, directed by Sadee, studies genetic factors that determine the activity of drug receptors and metabolizing enzymes, critical elements in a patient's response to most drugs in current use. The research is designed to identify clinically useful biomarkers that will help identify people who, because of their genetic make-up, respond to or metabolize drugs in ways that alter the drug's activity in the body, according to Sadee, a specialist in pharmacogenomics, a field that investigates the genetic basis for variations in drug response.

Some people, for example, may be genetically predisposed to respond to a particular drug to an unusual high degree. Such individuals would need a lower-than-usual dose of drug to avoid serious side effects. Other people may have genes that reduce drug response and may need a higher-than-usual dose to benefit from the drug. And some people may lack an enzyme entirely that is needed to metabolize a particular drug. These individuals are potentially at risk and should receive a different agent altogether.

"We are applying genome sequencing and other fundamentally new approaches to identify biomarkers that will make drugs more efficient and prevent side effects," Sadee says. The Sadee group has already identified a series of clinically promising pharmacogenetic biomarkers as potential guides in a person's therapy.

The 14 research groups within the PGRN are studying the effects of genes on people's responses to a wide variety of medicines. Each group is independently funded by the National Institute of General Medical Sciences and multiple other institutes of the NIH, and focuses on a particular area of pharmacogenomics.