Right-sized Medicine
DNA is often described as the genetic blueprint of life. Within the 3 billion A’s, T’s, C’s and G’s of the human genome lie clear specifications on eye color, bone structure, even intelligence. Those same instructions can also determine how an individual will respond to a particular drug therapy. This idea of tying genetic variation to drug response is the basis of pharmacogenomics, a field likely to revolutionize medicine.
Leading the effort to apply genetic knowledge to clinical practice is the UNC Institute of Pharmacogenomics and Individualized Therapy (IPIT), which celebrated its five-year anniversary with a symposium September 19 at the William and Ida Friday Center in Chapel Hill. The event featured presentations by the 2011 recipients of the IPIT Awards and concluded with a panel discussion on strategies for rationale therapeutics.
DNA is often described as the genetic blueprint of life. Within the 3 billion A’s, T’s, C’s and G’s of the human genome lie clear specifications on eye color, bone structure, even intelligence. Those same instructions can also determine how an individual will respond to a particular drug therapy. This idea of tying genetic variation to drug response is the basis of pharmacogenomics, a field likely to revolutionize medicine.
Leading the effort to apply genetic knowledge to clinical practice is the UNC Institute of Pharmacogenomics and Individualized Therapy (IPIT), which celebrated its five-year anniversary with a symposium September 19 at the William and Ida Friday Center in Chapel Hill. The event featured presentations by the 2011 recipients of the IPIT Awards and concluded with a panel discussion on strategies for rationale therapeutics.
On hand to congratulate IPIT’s director, Howard McLeod, Pharm.D., on the institute’s progress were Robert Blouin, Pharm.D., dean of the UNC Eshelman School of Pharmacy; Shelton Earp, M.D., director of Lineberger Comprehensive Cancer Center; and Barbara Rimer, Dr.P.H., dean of the UNC Gillings School of Global Public Health.
“One of the aspects of being a public university is that we are keenly aware of the expectation and the need to translate discoveries so that they benefit people,” said Dean Rimer. “We recognize the need to speed up that process by bringing in epidemiologists, biostatisticians, ethicists and people with expertise in nutrition and policy and health behavior to share their perspectives. In exchange, those experts get access to great data and get to be part of the scientific process. But they also have the opportunity to work with colleagues in a way that really sets Carolina apart -- the excitement of working with people in the cancer center and the CTSA [NIH Clinical and Translational Science Awards, at NC TraCS Institute] and all across the university. IPIT is a great example of what comes from such interdisciplinary excellence.”
In the five years since IPIT began, its investigators have secured 168 peer-reviewed grants, landing over $20 million in NIH funds as principal investigator or co-investigator. They have published 680 peer-reviewed publications, over 100 of which have appeared in journals with double-digit impact factors.
But to McLeod, the true benchmarks of success aren’t necessarily the academic ones. He listed four categories where he thought IPIT has excelled: recruiting new faculty, training the next generation of scholars, researching innovative ideas and changing clinical practice. McLeod gave an example of one innovative project where IPIT researchers are testing whether it is better to use genetic information or clinical information to choose what dose to prescribe of the popular blood thinner warfarin. Scientists have known for several years that patients with certain variants of the CYP2C9 and VKORC1 genes probably need lower initial doses. But despite FDA’s suggestion that pharmacogenomic testing might aid dosing, the use of such tests by prescribing clinicians remains controversial.
“One thing that was very impressive about Howard’s vision in creating IPIT was the absolute commitment to translate discoveries that were taking place in the laboratory to patients, and not just in the theoretical sense, but actually in creating programs that would make pharmacogenetics real to the patients we are here to serve,” said Blouin.
IPIT has developed a personalized medicine consultation service within North Carolina Translational and Clinical Sciences (NC TraCS) Institute to advise researchers interested in taking such research assays and pushing them forward into clinical assays that can be used to tailor medical treatment. NC TraCS is part of a national consortium created to turn discoveries into practical solutions for patients. McLeod says that focus on the patients is an extremely important aspect of both IPIT and the CTSA.
“The reason this concept of a multidisciplinary institute has been successful is because it brings together all different types of people to turn an initial discovery into a boring, routine, everyday type of finding,” said McLeod. “So if we take exciting science and prove it is useful, and prove that it is good for care, it will become routine, and that is the kind of boring that I like.”
Regardless, the rest of the IPIT anniversary symposium was anything but boring. The first invited speaker, Munir Pirmohamed, Ph.D., M.B. Ch.B., National Health Service Chair of Pharmacogenetics at the University of Liverpool, received the 2011 IPIT Award for Public Service because of his leadership in building the UK Pharmacogenetics network and his work in driving adverse-drug-reaction pharmacogenetics in Europe. The award also recognized his sustained efforts in the discovery and implementation of pharmacogenetics. Pirmohamed gave a talk on “Genetic Predictors of Adverse Drug Reactions.” He has found that compliance -- a huge issue in medical care -- can actually increase with the use of pharmacogenetic testing, because physicians are more confident in prescribing a particular drug and patients are more confident in using it.
Robert Epstein, M.D., president, chief clinical research and development officer at Medco Health Solutions, Inc., spoke next. Epstein received the 2011 IPIT Award for Patient Service because of his leadership in the effort to expedite the practical application of pharmacogenomics in applied programs by using information available in the Medco patient database to perform studies on drug response. He spoke on the topic “Determining Research Priorities in Pharmacogenomics at Medco.” As he explained it, Medco is an organization that works on the private side of public health, trying to make medicine work smarter. Epstein said that consumers, hospitals and insurance companies are spending more on adverse drug reactions than on the drugs themselves, an issue they could avoid with smart approaches like personalized medicine and pharmacogenomics.
Gary Puckrein, Ph.D., president and chief executive officer, National Minority Quality Forum, a not-for-profit organization he founded in 1998, spoke third. His forum addresses the critical need for strengthening national and local efforts to use evidence-based, data-driven initiatives to guide programs to eliminate the disproportionate burden of premature death and preventable illness for racial and ethnic minorities and other special populations. Puckrein gave a presentation titled “Adverse Reactions to Medications in a Consumer-Oriented Health System.” He explained that understanding geographical patterns of health issues and health inequities could improve the management of health care resources.
The symposium concluded with a lively discussion between the members of the audience and the panel of speakers on the future of the field. A couple of panelists suggested that large databases of genomic information from patients will help take pharmacogenetics to the next level. Epstein expressed concern, however, that such databases may just add to the plethora of T1, basic research studies.
“There are already a gazillion studies showing an association between some genetic variant and disease,” said Epstein. “What we need is some way to distill down all the stuff that is bottled up in T1, figure out what is worth focusing on, and then zero in on the right questions so we can use pharmacogenomics now. We can’t wait 5-10 years to use some of this knowledge – we are in a health care crisis and we need to use it now.”
