A step closer to personalized medication
Researchers last week announced that they had successfully used patients' genes to determine how much of a potentially dangerous blood-thinning medication they should get -- bringing the era of personalized medicine a giant step closer.
Personalized medicine, where patients get a diagnosis and treatment plan tailored to their genetic profile, has been a promise since the human genome was first sequenced five years ago. Doctors hope that one day patients' entire genetic profile will be placed on a single chip, and medications will be tailored based on that data for the rest of their lives.
Over the last few years, two cancer drugs -- first Gleevec and then Iressa -- have been shown to work better for people with certain genetic profiles. But last week's report, published in the New England Journal of Medicine, marks the first time the approach has worked for determining drug dosage.
''To me, it's really remarkable that five years after the sequencing of the human genome we're starting to see direct applications for clinical medicine," said Dr. Scott Weiss of Brigham and Women's Hospital who conducts research into personalized asthma treatments. ''The major areas are going to be in prediction -- of who gets disease, and for those who have it, predicting the course of their disease, and predicting who's going to respond to medication."
The blood-thinning drug warfarin (sold under the prescription Coumadin) is notoriously hard to prescribe, with many patients, given just a bit too much, bleeding internally, and others, given too little, left at risk for blood clots. The researchers at the University of Washington in Seattle and Washington University in St. Louis said they had found a way to use the patients' genes to determine whether to start them on a high, medium or low dose of the drug that is now used by millions of Americans at risk for blood clots or heart attacks.
The researchers studied a gene called VKORC1, which manufactures a protein that controls clotting and is targeted by warfarin. They found that mutations within VKORC1 played a key role in how patients reacted to the drug. Some with certain mutations required higher doses, and others with differing mutations needed far less.
''We found that 25 percent of the [overall] variance in warfarin dose is due to this one gene," said the Allan E. Rettie of the University of Washington. ''This is possibly the single biggest contributor to variability in people's responses to the drug and could be a central factor in setting the initial dose."
The team said more work would have to be done before doctors could use their findings to routinely calibrate warfarin doses for patients. But given the widespread use of the drug, their paper was seen as a major advance in this new field, known as pharmacogenetics.
''This research points to the value of pharmacogenetics," Elias A. Zerhouni, director of the National Institutes of Health, stated in a release. ''It shows one important way in which we are beginning to apply knowledge about the human genome for treating disease and improving human health."
Similar work is going on in Boston on asthma. Weiss believes patients could be better matched to one of the two major asthma treatments, inhaled corticosteroids or inhaled beta-2 agonists. More than 15 percent of patients don't respond to the drugs.
Weiss's team is looking for genetic mutations that signal the drugs to which patients will better respond, and how much they need. Weiss said he told officials at the National Institutes of Health, which funds his work, that he would have the answer -- and a test for patients -- ready within five years, saying, ''I think we can do it."
At the Dana-Farber Cancer Institute, oncologist Todd R. Golub has been at work on bringing pharmacogenetics to the treatment of acute leukemias and lymphoma. But there is a twish: Instead of searching patients' genes, he searches the genes of tumors -- cancerous tumors are driven by mutated DNA. That way, he said, tumors can be classified more specifically and treatment calibrated.
''I think there's a general expectation that in the future this kind of molecular classification and diagnosis of cancer is going to be the mainstay," Golub said. ''I think it's very much going to transform cancer. How long it will take, I don't know for sure."
Rochelle Long can see the progress from her perch as program director for NIH's Pharmacogenetic Research Network, the nation's chief funder of personalized medicine research, which has spent more than $100 million in the last five years on the work.
''There are people looking at cardiovascular drugs, anticancer drugs, antidepression drugs," she said of studies funded by her agency. ''It's exciting; there's a lot of research going on."
And Long still believes in the future of pharmacogenetics: ''The promise is ultimately getting a genetic test just once, and knowing how you will interact with most drugs for the rest of your life."
