On Target
A new generation of drugs offers customized cures
Anticlotting. The next test to travel this route may be one for reactions to the anticlotting drug warfarin. Warfarin is one of the most frequently prescribed medications for heart patients, but at too high a dose it can cause uncontrolled bleeding, requiring hospitalization and emergency transfusions. "So doctors monitor patients who take the drug pretty carefully," says David Veenstra, a drug outcomes researcher in the pharmacy department at the University of Washington in Seattle. Given that kind of care, Veenstra was surprised to find one group of warfarin patients with twice the bleeding risk of others. The high-risk patients turned out to have variations in a gene called 2C9, which codes for a liver enzyme that removes warfarin from the body. As Veenstra reported last year in the Journal of the American Medical Association, these variants make for a slower-acting enzyme, which in turn makes for more warfarin and more bleeding. The test is fairly straightforward. "I'd encourage patients to get this screen, and I'd certainly use the data," says Baylor's Roberts. "But most cardiologists haven't grown up with genetics, and they're not familiar with it."
They'll probably get to know it well in the next couple of years, many in the field predict, along with another test for sensitivity to blood pressure medications. Three months ago, Julie Johnson of the University of Florida presented data at an American Heart Association meeting indicating that people have different forms of a receptor that takes up drugs called beta blockers. Some forms produce no response to the drugs, and some produce a good response. "Those with the no-response variant obviously should try a different drug," she says. She's trying to replicate the finding in a larger study. If the receptor test does indeed have value, "we should be able to get away from trial and error and predict good responses to drugs using genetics."
But leaving errors behind and hitting the targets more precisely may call for more than larger clinical trials. It may require changes outside the lab and the clinic. A lot of those changes involve how medical care is paid for. If you're an insurance company, asks Roberts, would you pay for a test predicting someone's response to a heart drug? The way people switch health plans so often, it's likely that the prediction will benefit some other insurer--as well as the patient, of course. Plus there are the often-discussed issues of genes and privacy. What's to prevent your insurance company from boosting your premiums if your genes put you at risk for hypertension? After all, they would boost the charges if you smoke. "This country has to come to grips with the implications of this science," Roberts says.
The science, for its part, is moving ahead, clarifying the roles of the myriad genes involved in disease. "It's like when Galileo made the high-powered telescope," says the National Cancer Institute's Sausville. "All of a sudden people could see things around planets, like moons, that hadn't been thought about." But thinking about them opened up a whole universe of ideas.
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