Research shows hope for tailored medicine

Initiative focuses on sequencing of genomes

Imagine if you could carry a credit card-size record of all the 3 billion A’s, T’s C’s and G’s that make up the alphabet soup of your genome. A simple swipe of the card could inform your physician right away if a drug being considered will help or hurt you.

This is the kind of promise behind President Barack Obama’s $215 million initiative to develop personalized medicine.

“We’ve arrived at the point where this could happen, and is going to happen,” Francis Collins, director of the National Institutes of Health, said at a recent biotechnology conference in Philadelphia.

A newly published study by researchers at the University of Pennsylvania is another step on the path.

The study, which appears this month in the journal Cell, came from a curious case regarding a class of anti-diabetes drugs known as TZDs. They are highly effective in some people. But for 20 percent to 30 percent of patients, they are useless and can cause serious side effects.

The Penn team had a hunch that the variation could have something to do with small differences in the regions of the genome that control whether a gene will be switched off or on, much like a light switch.

These areas work by lighting up genes when a molecule known as a nuclear receptor attaches to DNA.

Many drugs on the market, such as TZDs, work by binding to nuclear receptors, which regulate whether genes are turned on. The Penn researchers found that one change in the sequence of base pairs — adenine, thymine, cytosine and guanine, those A’s,T’s, C’s and G’s — in the light switch regions of the genome ultimately might predict how those drugs will affect a patient.

“Every drug has a risk of some sort,” said Mitchell Lazar, professor of medicine and genetics at Penn’s Perelman School of Medicine and senior author on the study.

Figuring out how those risks are related to a person’s genetic code is “one of the principles of personalized medicine.”

“The cost of determining a person’s genome is coming down to the point where it’s widely predicted that in five to 10 years, every person will be able to have their genome sequenced,” Lazar said. “Epidemiologists and statisticians will be able to correlate individual differences in the genome and ask, ‘Was the drug effective?’ “

Finding the mutations that matter is the hardest part, said Tim Reddy, assistant professor of biostatistics and bioinformatics at Duke University, who was not involved in the Penn study.