Of course children don’t worry much about heart attacks. But what if there were a test that could predict how vulnerable a child was to cardiovascular disease later in life? Then doctors might be able to counsel their patients about making lifestyle changes, or give a child preventative medicines before their arteries started clogging up.
That’s the dream of pharmacogenomics – the practice of tailoring treatments to any individual’s unique genetic make-up. Since the completion in 2003 of the human genome – an entire readout of the sequence of nucleotides in human DNA – this emerging field of medicine has been dogged by skepticism and unmet promises. But as pharmacogenomics tests and treatments are starting to materialize and technological advances in the laboratory are speeding development even further, once-doubtful drug companies are beginning to get on board.
“The level of interest has definitely heightened. People are no longer asking, ‘is this for real?’” says Lawrence Lesko, director of the office of clinical pharmacology and biopharmaceutics at the U.S. Food and Drug Administration in Rockville, MD. “This year there is more of a discussion of how long it will take, rather than will it work.”
Thomas J. White, vice president of research at Celera Diagnostics in Alameda, CA, is one of the researchers trying to turn pharmacogenomics into more than an exotic tongue-twister. His team has extracted data from thousands of patients and assembled a selection of tiny genetic variations – usually in the form of flipped nucleotides, also known as a single nucleotide polymorphisms, or SNPs – that influence a person’s risk of heart disease. Researchers can then convert these variations into a cardiovascular risk score, which could one day be used as a diagnostic test.
According to Celera’s findings, presented at a Scientific American’s Targeted Medicine 2005 meeting in New York last week, people who carry two or more of these variations have a 70 percent greater chance of having cardiac trouble than those with fewer of the variations.
“It’s still early, but this could take the place of family history,” says White. “If your father has heart disease, you don’t know what that means for your own risk, because only half your genes came from him.” White is now analyzing the results from clinical trials of the popular cholesterol-lowering drugs known as statins, to see if the same risk factors can predict who will respond best to the drugs.
Some of the genetic variations that influence diseases and patients’ responses to treatments are simple. Last year, for example, scientists discovered small genetic changes in a key enzyme that make the cancer drugs Iressa and Tarceva much more effective in people who carry the mutation. And, in January 2005, the FDA approved a diagnostic test, produced by Swiss drug-maker Roche, that predicts how people with different variations in the DNA that codes for two enzymes will metabolize many popular drugs.