April 23, 2015

Lecture explores efforts to move pharmacogenetics into the clinic

Preemptive genotyping: It sounds like a surprise attack, and it is.

Preemptive genotyping: It sounds like a surprise attack, and it is.

If the genotype, or “read-out” of the patient’s genes, was in the medical record along with the EKG and blood work, doctors would know in advance which drugs would be most effective and would have the fewest side effects. Disease wouldn’t stand a chance.

That’s the future. But, increasingly, the future is now.

Last week at Vanderbilt during the annual Grant R. Wilkinson Distinguished Lecture in Clinical Pharmacology, Mary Relling, Pharm.D., described what is being done to move pharmacogenetics, the study of how genes affect a person’s response to drugs, into the clinic.

Mary Relling, Pharm.D., talks about the quest to bring advances in pharmacogenetics to the bedside. (photo by Susan Urmy)

One effort is national, the Clinical Pharmacogenetics Implementation Consortium, or CPIC, which Relling and Stanford University’s Teri Klein, Ph.D., co-founded in 2009. Vanderbilt’s Dan Roden, M.D., assistant vice chancellor for Personalized Medicine, is a member of the CPIC steering committee.

“Our goal is to create freely available guidelines that translate into actionable prescribing decisions,” said Relling, chair of the Department of Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis. “That really makes preemptive genotyping a possibility.”

The other is local. Pharmacogenetics for Kids or PG4KDS is a St. Jude project that is incorporating the new guidelines into “routine” patient care.

“The sequence is already there, just like age and body type and sex,” she said. “How are you going to use it in the clinic?”

Relling discussed how pharmacogenetics can potentially improve the treatment of acute lymphoblastic leukemia (ALL), the most common childhood cancer.

Glucocorticoid is one of a number of drugs that can cure ALL, but because it also interrupts the bone’s blood supply, it can cause osteonecrosis, death of weight-bearing bones. “Many of our children need to have hip replacements before they finish their two-and-a-half years of chemotherapy,” she said.

Researchers now know many of the risk factors for osteonecrosis, including age — older children are more vulnerable — and how quickly the liver breaks down the drug. “Our goal is to better understand the mechanisms of these adverse effects and then to develop means to avoid them,” she said.