"I noticed a difference the next day," says Caitlin O'Hara, 29, who was diagnosed with cystic fibrosis at age 2 and was able to access the twice-daily pill through Vertex's compassionate use program when her lung function was too poor to get her into a clinical trial. O'Hara had had a relatively normal childhood, except that she needed IV antibiotics every couple of years, and a surgery to treat infection, a common problem for CF sufferers. But in her mid 20s, her symptoms worsened. "I had to cancel trips all the time, because I was too sick. I was avoiding any situations where I'd unexpectedly be asked to walk," she says.
Two weeks after she started the drug, a pulmonary function test confirmed she was improving. "I haven't been in a hospital in two years," she says. "And a year after starting the drug I went to Paris for two weeks by myself, which is something I never thought I'd be able to do unless I got a lung transplant." That still may be necessary eventually. But meantime, "I can live my day-to-day life," she says.
While CF is triggered by changes in just one gene, challenges like coronary artery disease, type 2 diabetes and depression are far more complex, the result of an as-yet-undetermined combination of genetic predisposition and environmental influences. Individualized treatment regimens may be options someday, when more is known about the diseases. And researchers hope that some of these ailments, including cancer, can be avoided. Could we ever get an individualized prescription for prevention? "That's the trillion-dollar question," says Peter Tonellato, director of Harvard's Laboratory for Personalized Medicine.
At this point, researchers are hunting for genetic variants that might be associated with an elevated risk of disease. A team led by Sekar Kathiresan, a genetics expert and director of preventive cardiology at Massachusetts General Hospital, has discovered 45 different genetic variants that can identify a subset of people who have a greatly increased risk of a heart attack. If borne out by future research, those at high risk might someday be told to take aspirin and statins earlier in life, while those not high risk could be advised to wait, he says.
Also ripe for personalized prevention is Type 2 diabetes. About 25 different genetic variants raise the risk of the disease, but even knowing that information isn't a particularly good predictor of whether someone will come down with it, says Allen Spiegel, endocrinologist and dean of the Albert Einstein College of Medicine of Yeshiva University. More finely honed predictors could identify the people who need intensive help to change their diet and exercise habits or who should take medications to prevent the onset of diabetes.
One researcher provides a futuristic glimpse of what this analysis might look like if extended beyond genomic sequencing to other "omes" like the proteome (the proteins produced by the human body) and metabolome (chemicals). Michael Snyder, director of the Stanford Center for Genomics and Personalized Medicine, had his genome sequenced and underwent frequent blood draws to measure thousands of molecules in his blood. His genome predicted an increased risk of Type 2 diabetes, which didn't really worry him because he was at a healthy weight and didn't have other risk factors. But his glucose levels soon spiked, and he was diagnosed with the disease.
"I changed my eating habits a lot" and exercised more, says Snyder. Six months later, his glucose levels had returned to normal.
Snyder foresees a time in preventive medicine when gene sequencing is routine and regular blood tests can capture many more pieces of information than the number of white or red blood cells or your blood glucose level. To be sure, his is a research project with a single subject – himself – so a lot more work needs to be done. Snyder is also now tracking his microbiome (the microbes that live on and in the body) and epigenome (chemical changes to the DNA that can be triggered by the environment). Whether this kind of personalized information, collected and used on a larger scale, could improve care or lower costs is still a question for the future.