Wednesday, November 01, 2006

Still Waiting for Personalized Medicine

Pharmacogenomics promises to let doctors choose drugs and dosages based on tests of your genetic profile. But just try taking a test.

By Emily Singer

Nausea, fatigue, dizziness, dry mouth, insomnia. For people like me, who seem susceptible to every side effect possible, the tiny type on ads for new drugs is required reading. NyQuil puts me into a half-conscious delirium. Codeine makes me throw up. And back in college, when my doctor prescribed Wellbutrin to help me quit smoking, I experienced blurred vision and the worst headaches of my life.

Given that my troubled history with medication is shared by my mother and sister, I have long suspected a genetic basis for my sensitivity. So like many others, I have over the last few years eagerly anticipated the benefits of pharmacogenomics--a field whose researchers aim to let doctors tailor prescriptions to their patients' genetic makeups. It's one of the most tantalizing promises of the genomic era: quick and easy tests that tell you which drugs to take or what dose is right for you.

A few tests have been developed for specific diseases, such as cancer--most notably a genetic test that predicts which lung cancer patients will respond to some medications. But a new product, marketed by the Swiss pharmaceutical giant Roche and approved by the U.S. Food and Drug Administration in January 2005, now has the potential to begin making pharmacogenomics broadly accessible. Called the AmpliChip CYP450 assay, it uses genetic analyses to ascertain how quickly people metabolize certain drugs, thus predicting who is most likely to experience unpleasant or even toxic side effects.

When two people take the same dose of a drug, their bodies may metabolize it so differently that the amount of it that can act on its target varies tremendously. Some people may have an especially efficient form of an enzyme that breaks down a drug; others may have a less functional version. The AmpliChip test works by detecting specific variations in genes that code for two important drug-metabolizing enzymes, CYP2D6 and CYP2C19. These enzymes help break down 25 percent of all drugs, including the most commonly prescribed drugs in the United States, such as antidepressants, blood pressure medicines, cough medicines, and painkillers.

People with genetic variations that give them less efficient versions of the enzymes, known as poor metabolizers, could have high levels of a drug in their body for a longer period, increasing the potential for side effects. People with functioning copies of the genes are called extensive metabolizers, while people with extra copies of the functioning CYP2D6 gene are labeled ultrarapid metabolizers. "This kind of information is something every doctor seeing patients should know about," says Julio Licinio, a psychiatrist at the University of Miami's Miller School of Medicine and the editor of The Pharmacogenomics Journal.

CYP2D6 variations occur relatively frequently in the gene pool, though the incidence differs by population group. About 5 to 10 percent of Caucasians have a genetic profile that makes them poor metabolizers of drugs broken down by CYP2D6, whereas among Asians, the proportion is more like 15 to 20 percent. And almost 30 percent of people from North Africa and the Middle East are ultrarapid metabolizers, meaning they may need higher than standard doses of various drugs.