Dr. John A. Oates, left, and Dr. Dan M. Roden at the symposium last week. (photo by Paul Hightower)
Oates Institute launched
In the not-so-distant future, we may be adding another card to our wallets – a gene card that describes our individual genetic variations, the tiny changes in our DNA that affect how we respond to medicines or that make us susceptible to certain diseases.
The “gene card” idea was discussed by speakers last week at the first annual John A. Oates Symposium in Experimental Therapeutics. The day-long symposium focused on pharmacogenetics – the impact of genetic variation on an individual’s response to drugs – and launched an institute named in honor of Dr. Oates, Thomas F. Frist Professor of Medicine and founder of the division of Clinical Pharmacology. Pharmacogenetics will be a major area of investigation in the new John Oates Institute for Experimental Therapeutics.
“With the genetic revolution and the rapid advances in molecular science, this is a time of great opportunity for clinical investigation and for the Institute for Experimental Therapeutics,” Oates said. “I look forward to the discoveries that are made in the institute and to its contributions that bring safer and more effective therapy to our patients.”
The idea that genetics control drug response is nothing new to Vanderbilt investigators, said Dr. Dan M. Roden, William Stokes Professor of Experimental Therapeutics and director of the division of Clinical Pharmacology. The Oates Institute will serve as a springboard for moving the study of drug action beyond the division of Clinical Pharmacology into the general culture of the medical center, he said.
“The institute’s goal is to promote interdisciplinary research to understand variability in drug action in human beings, to improve therapy with existing agents, and to develop new drug targets,” Roden said.
Speakers at the symposium highlighted some of the shortcomings of currently available medicines. The pharmaceutical industry “has been committed to developing one-size-fits-all drugs,” said Grant R. Wilkinson, Ph.D., professor of Pharmacology. But the variations in how drugs affect individuals continue to challenge the industry. Over 2 million Americans are hospitalized each year because of adverse responses to drugs, and 100,000 die. In recent years, at least six promising new drugs have been withdrawn from the market after widespread use showed serious side effects.
The promise of pharmacogenetics is that variations in certain genes can be used to predict who will have a favorable response to a drug, who won’t respond at all, and who will suffer serious side effects. Most speakers also used the term pharmacogenomics, to suggest that the combined effects of variations in many genes might predict responses.
Pharmacogenetics already guides clinical practice in the treatment of leukemia with thiopurine chemotherapy drugs. Patients who have a genetic variation in one of the enzymes responsible for metabolizing thiopurine drugs can suffer life-threatening side effects if they are given standard doses of these drugs. The solution – identify patients who have the variation and only give them five to 10 percent of the normal dose, said William E. Evans, Pharm.D., deputy director and executive vice president of St. Jude Children’s Research Hospital.
“We routinely phenotype or genotype every patient to determine the proper drug dosage,” he said.
Single genetic variations that profoundly affect drug safety or effectiveness, like the thiopurine example, will likely be the exceptions, the symposium speakers agreed. More likely are constellations of gene variations that affect response, with each alone having only minor effects. These will be more difficult to identify and will challenge current abilities to correlate genetic variations and drug responses.
Symposium speakers from the pharmaceutical industry expressed the hope that pharmacogenetics will speed up and reduce the cost of drug development. Restricting clinical trials to those patients who – based on genetics – should respond to a drug without suffering adverse effects will make trials safer and more cost effective and may move the drug development process more quickly to FDA approval.
But you won’t need to look for your gene card application in the mail any time soon. “It is an open question at this time whether prescribing by genotype will be a successful approach,” said Wilkinson.
Speakers in the symposium included Wilkinson; Evans; Dr. Richard M. Weinshilboum, professor of Medicine and Pharmacology at the Mayo Clinic; Dr. Jeffrey M. Drazen, professor of Medicine at Harvard Medical School; Denis M. Grant, Ph.D., senior director of Pharmacogenetics at Orchid BioSciences, Inc.; and Brian Spear, Ph.D., director of Pharmacogenetics at Abbott Laboratories.
The launch of the John Oates Institute for Experimental Therapeutics and the first annual symposium were supported by Merck and Company.