The transplant has by no means solved all of Nic's problems. He developed encephalitis and has a seizure disorder, his mother says. He continues to grow more slowly than his peers. He will need more reconstructive surgeries. But for now, at 8, he is active in a way his mom couldn't have imagined just a few years ago.
"We're completely amazed," she says. "Before, he couldn't walk, climb or jump. Now he has more energy than the entire household." Howard Jacob, director of MCW's Human and Molecular Genetics Center, says 19 children have now had their genomes sequenced, leading to five different diagnoses.
Unlike Nic's mysterious programming, the gene controlling cystic fibrosis, CFTR, has been known since 1989. The disease is caused by a variety of mutations in CFTR, which affects salt and water flow in and out of cells, and impacts various organs including the lungs and pancreas. Vertex Pharmaceuticals has developed a drug targeting one of those mutations and is studying whether, used in combination with other drugs, it could also provide a boost to patients with different genetic mistakes.
"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.