PROFILE: Personalized Medicine Energizes Tracy Glauser
How can physicians ensure that the medications they prescribe are the most effective choice for the children they treat?
For pediatric neurologist Tracy Glauser, MD, of the Cincinnati Children's Division of Neurology, that's the fundamental issue that drives both his research and patient care activities. As his career has evolved over 12 years at Cincinnati Children's, he continues to ask new questions.
"I came here with a focus on doing clinical trials for epilepsy drugs. But then I took a step back and said, 'I want to make a bigger difference.' Dr. Boat [director of the Cincinnati Children's Research Foundation] supported me, so I was able to obtain a National Institutes of Health training grant to retrain as a pharmacogeneticist. This has allowed me to look at the more fundamental issues of epilepsy, and everything flows from that," Dr. Glauser explains.
He notes that many of the older and newer medications designed to control seizures do that job well, but they also produce a variety of side effects. "There's a general push to establish evidence on which antiepileptic drugs are the best for kids. I was part of two studies that just came out comparing new medications in treating newly diagnosed epilepsy and cases that have proven difficult to manage," Dr. Glauser says. Coming soon from the International League Against Epilepsy is another study comparing the new and old drugs that he also co-authored.
The Case for Personalized Medicine
Although the studies produced valuable guidelines for physicians, they also uncovered another truth. "There's not as much evidence as we would like to make rational treatment decisions. So when the evidence is lacking,we need to turn to personalized, or individualized, medicine," Dr. Glauser explains. That's possible through two new areas of medicine. Pharmacogenetics focuses on how an individual's genetic makeup contributes to his or her response to a drug. Pharmacogenomics studies whether there's a pattern of gene expression, or a gene signature, that allows doctors to predict who will respond well to a drug – and who won't.
Dr. Glauser recently led a study examining the blood genomic expression pattern associated with valproic acid (VPA), a commonly used anticonvulsant with multiple systemic effects. Patients who did well on VPA had a specific recognizable pattern of gene expression, demonstrating that the medication does, indeed, turn genes on and off. Eventually,we'll learn what patterns of gene expression are associated with favorable responses or toxic responses to certain drugs. We probably won't see real results in pharmacogenomics for at least three to five years," he says.
Pharmacogenetics Arrives
On the other hand, pharmacogenetics is here now.This summer, Cincinnati Children's begins offering physicians a new service to optimize medication dosages for their patients.Testing and analysis for a wide variety of common drugs will help clinicians identify patients at risk for adverse drug reactions based on their genes."The pharmacogenetic testing provides a two-day turnaround and our multidisciplinary team can consult with physicians about their patient's test results. We're offering the only pediatric pharmacogenetic service in the United States," Dr. Glauser explains.
Cincinnati Children's can claim another first, thanks to Dr. Glauser and his team. In September 2003, the medical center was awarded a $17.3 million NIH grant for a study of childhood absence epilepsy.The grant is the largest ever for a pediatric epilepsy study, and the clinical trial will be the largest head-to-head randomized double blind drug trial ever conducted for pediatric epilepsy. Included is funding for pharmacogenetic and pharmacokinetic (the study of how a drug's level in the body changes during the day) research.
This son, grandson, brother and husband of physicians admits that finding time to sleep is not his highest priority. When he's not working, Dr. Glauser is spending time with wife Lisa Lewis, MD, an emergency medicine physician at Cincinnati Children's, and his 10- year-old and twin 5-year-old sons. The couple came to Cincinnati from St. Louis "so we could both practice at a top-flight medical center," Dr. Glauser says,"and we've stayed because of the outstanding people, the great community life and the wonderful resources and visionary people at Cincinnati Children's.
"It's not often that you have the opportunity to make a fundamental improvement in how we practice medicine.That's why I love coming to work every day."
Dr. Glauser is associate professor of pediatrics and neurology in the Division of Neurology and director of the Comprehensive Epilepsy Program at Cincinnati Children's. His papers on the efficacy of new antiepileptic drugs were published in Neurology (62:1252–1260, 2004 April and 62:1261–1273, 2004 April). His paper on valproic acid genomic expression was published in Acta Neurologica Scandinavica (109[3]:159-168, 2004 March) and supported by grants from the National Institutes of Health.
