Sep. 11, 2012 at 11:38 AM ET
Abbygail Ainslie was born perfect in July 2011. She weighed nine pounds and the genetic tests that have become standard at most hospitals showed no problem whatsoever. But her mother, Jessica Ainslie, didn’t feel right.
“She was a beautiful baby girl,” Ainslie, who lives in Peoria, Arizona, told NBC News. “We got her tested and the pediatrician said, 'Yeah, everything looks good’,” she added. But everything wasn’t good. Ainslie’s son Colton had been born with a rare genetic disease called severe combined immune deficiency syndrome (SCID), and she knew Abby had a one in three chance of having it, too.
Sure enough, specialized genetic testing done at Duke University confirmed Ainslie’s fears. Abby had the same form of SCID, often called "bubble boy disease" after the case of 13-year-old David Vetter, who died in the 1970s after living in a plastic isolation ward.
Colton and Abbygail are among three children successfully treated for their immune deficiency during an experiment detailed in Tuesday’s issue of the journal Blood. Ainslie says she never doubted her decision to have Abbygail, despite the risks.
“I could have brought her home and we could have lost her,” says Ainslie. But she had a trump card in her back pocket. Colton, who is now 5, had been treated for his SCID using an experimental gene therapy approach.
“So of course I called Dr. Kohn and said, ‘hey, are you ready for another one’?”
Dr. Donald Kohn, a professor at UCLA’s Department of Microbiology, Immunology and Molecular Genetics, was. He’d been helping run a clinical trial – early-stage testing of new treatments – for gene therapy for SCID. SCID is a catch-all name for a number of genetic immune deficiency syndromes that affect about one of every 100,000 newborns.
Abby and Colton both had a type called SCID-ADA, which account for about 15 percent of SCID cases. Their bodies produce a faulty version of an enzyme called adenosine deaminase or ADA. Without it, immune cells die. Most patients die by the time they are about 2 from some infection, because their immune systems just can’t fight off germs.
Ainslie saw it with Colton, who was born prematurely, at 26 weeks, but seemed to have recovered– at first.
“Then all of a sudden he started getting this cough. Then he started vomiting a lot. Then I started noticing he wasn’t keeping anything down,” said Ainslie, now 28. He had bad thrush, and Ainslie made repeated trips to the emergency room.
“The doctors were like, ‘He’ll be fine. We’ll just hydrate him’,” Ainslie said. Later, “they labeled him ‘failure to thrive’,” she added. “Hearing those words, I wanted to give up.”
Some doctors told Ainslie it was nothing serious, but she pursued testing. “They finally came up with severe combined immune deficiency-ADA,” she said. “At first, I didn’t know what it was.” Colton was air-evacuated to Children’s Hospital in Los Angeles and Ainslie and her husband Michael followed. This gave her time to research.
“Never go on the Internet to figure out what your kid has,” Ainslie said. “I went on the Internet and I was freaking out.” She was sure Colton would die. The current treatment is to regularly dose kids with the ADA enzyme, but the treatment doesn’t work well and it is very expensive.
Kohn enrolled him in the clinical trial being reported Tuesday in the journal Blood. Kohn and colleagues tried gene therapy on 10 U.S. children, including Colton and Abbygail, eventually tweaking the method so that it worked. Three of the kids are now healthy.
Gene therapy sounds simple. If a patient has a disease caused by a single mutated gene, just replace the bad gene and everything should be all right. But it’s not so simple. For one, it’s hard to get a new gene into the body, to get cells to take it up and use it. Scientists mostly use viruses to get the job done, because viruses infect by invading cells and injecting their own genetic material.
But the viruses can cause trouble, even seemingly harmless ones. In 1999, 18-year-old Jesse Gelsinger died during a gene therapy clinical trial when his immune system overreacted to the virus being used to carry the new gene into his body. And when French and British doctors first tried gene therapy for SCID a few years later, they cured a few infant boys, but five have developed leukemia as a result –although the leukemia was relatively easy to cure.
And the body doesn’t always hang on to the new gene, or sometimes the gene gets inserted into a place where it doesn’t work. And in the cases of kids with SCID-ADA, it wasn’t clear why, but the gene therapy did not seem to be helping. Kohn’s team, led by Dr. Fabio Candotti at the National Institutes of Health, was tweaking the approach. European researchers had treated 10 children with SCID-ADA but U.S. researchers had not succeeded.
The researchers in Europe had used chemotherapy to kill off immune cells in the patients’ bone marrow, effectively giving doctors a clean slate to try the gene therapy on. But this approach worried Candotti. “These patients are fragile to start with and adding chemo to their current medicine may be dangerous,” he said.
It turns out this was mistaken. The first four U.S. kids who got gene therapy, without chemo first, weren’t helped. By the time Colton and Abbygail were treated, the researchers had the formula down. They gave low doses of chemotherapy and stopped giving the kids any infusions of the ADA enzyme.
“This step proved to be important,” Candotti said. “By adjusting the chemotherapy dosage, we found its optimal level for enhancing the efficacy of the corrected stem cells.”
Abby seems to have done better than Colton, perhaps because she was an infant when treated, while Colton was a toddler. Colton will require regular infusions of an immune booster called IVIG, probably for life, while Abby doesn’t seem to. “She is doing fantastic,” Ainslie says.
“This is the first time this disease is cured in the U.S. ,” Candotti said. He cautions that Abby and Colton are rare and lucky children. “It is not ready for prime time in the sense that it is not available in all centers,” he said.
And it’s expensive. “We did a back-of-the-envelope calculation. We think it is costing around $200,000 for treatment,” Candotti says.
Ainslie said most of the expenses were covered because Colton and Abby were taking part in a clinical trial. But she and Michael had to pay for most of their own travel between Arizona and Los Angeles and other expenses.
Ainslie is keenly aware that other parents may criticize her and Michael, who is 32 and in the Navy reserve, for having a second child they knew could be at risk.
“I wanted another child,” she says. “I think you always take a chance. You take a chance driving on the road. You take a chance with anything in life. But on the other hand, I knew if she had SCID she’d be in great hands.”
In June, Doreen Flynn came under criticism when she fought to change the law to allow bone marrow donors to be paid. She has three daughters who have a genetic disease called Fanconi anemia, which can be treated with bone marrow transplants. Some questioned her decision to have more children after learning the first had an inherited genetic disease.
Ainslie understands. “I definitely prayed,” she said. “We both decided we were going to have one more and life would not be the same if I didn’t have her.”
Abby is now more than a year old, and Colton started kindergarten in August.
“He is a big boy now,” Ainslie says. “Seeing him go to kindergarten was really, really, emotional for me because I never thought he would make it there. Going to school, it is one of those things I can check off my list.”