‘It gave me my life back’
After years of pain from hemophilia, Pitt study changed his life
About six years ago, Dan Price and his family attempted a short vacation to the Columbus Zoo. Because it was relatively close to home, Mr. Price didn’t bring medicine to treat his hemophilia. But by 3 a.m., he was suffering from ankle pain so unbearable that he left his hotel room to find a hospital in Columbus that could inject him with a clotting factor.
When Mr. Price tells stories of his life more than five years ago, he often prefaces them with “before.” As in, before he was able to kick a soccer ball with his sons. Before, when he worried that he wouldn’t physically be able to continue doing his job as a paramedic. Before he enrolled in a study about gene therapy and hemophilia through the University of Pittsburgh.
Five years after receiving one gene therapy injection in a room at UPMC Montefiore as part of the study, Mr. Price hasn’t needed a single hemophilia treatment. His body now knows how to produce a clotting factor on its own, essentially curing his hemophilia.
“It’s been amazing,” said Mr. Price, 50, of South Franklin in Washington County. “It gave me my life back.”
Mr. Price has hemophilia A, the most common type, which affects roughly 1 out of every 5,000 males worldwide. Those with severe hemophilia A produce less than 1 percent of normal levels of a protein called factor VIII, meaning that their blood doesn’t clot normally, which results in uncontrolled bleeding, severe joint pain and a higher risk of death.
Results of the study that Mr. Price took part in, which involved researchers at the University of Pittsburgh, the University of Pennsylvania and Penn State – as well as in Australia, Mississippi, Massachusetts, New York and Oregon – were published in November in the New England Journal of Medicine. Of the 18 patients who participated, all but two had lasting effects from the gene therapy that enabled their bodies to produce their own factor VIII. The participants had more than a 90 percent reduction in bleeding episodes, from an average of 8.5 each per year before the gene therapy to an average of 0.3 each per year after.
“This is the first time that gene therapy has been shown to correct hemophilia A with a safe and effective outcome,” said Dr. Margaret Ragni, an author of the study and a professor of medicine and clinical translational research at the University of Pittsburgh. “It provides promise for other genetic disorders.”
Because hemophilia A is a genetic disease, passed from mother to son, Mr. Price’s parents knew even before he was born that there was a chance he’d inherit the disease. He remembers long, regular trips as a child from his home in rural Washington County to Children’s Hospital of Pittsburgh, where he would spend hours getting infusions of a plasma product and other therapies. Mr. Price was never permitted to play sports as a child because of the dangers of bleeding and joint pain, although he was active in marching band and on his parents’ and grandparents’ farms.
While hemophilia can be painful and dangerous, it’s not necessarily in the way that people think. “The common misconception is that if you cut yourself shaving you’re going to bleed to death,” he said. And while that’s not true — Mr. Price suffered serious cuts growing up on a farm without major consequences — certain injuries like cuts in the mouth can be dangerous because of difficulty healing, as well as what he calls “epic nosebleeds.”
As with many hemophiliacs, the biggest impact on Mr. Price’s quality of life came from joint pain, caused by internal bleeding. By his early to mid 40s, “every time I got out of a chair it was pain. I woke up, pain. It was just pain 24/7,” he said. “My ankle had deteriorated to the point where I was ready to saw the darn leg off. I thought, having an artificial foot has got to be better than this.”
He would sometimes work his entire shifts at his job as a Peters Township paramedic from the garage rather than face the pain of walking up steps to the
office. Doctors were considering fusing Mr. Price’s ankle because he didn’t have much mobility anyway.
He was also getting timeconsuming infusions of factor VIII multiple times per week to dull the pain caused by internal bleeding. And while he no longer had to go to the hospital for treatment, as he did as a child, he would often drive to his work to have one of his coworkers do it rather than limit himself to the veins he could find at home onehanded.
Even before gene therapy, hemophilia treatment had come a long way. In the early 1900s, when the life expectancy for a hemophiliac was just 12 years old and there was no way to store blood, treatment was limited to whole blood donations from family members. Various treatments were tried in the years since, from diluted snake venom to peroxide to gelatin, until scientists discovered transfusions of plasma, which became common in the 1940s and 1950s. But even in 1960, the life expectancy for a hemophiliac was less than 20 years old.
The 1970s and 1980s brought advances in using thawed frozen plasma, as well as freeze-dried powder concentrates that could be administered at home. But hemophiliacs in the 1980s were devastated by the AIDS epidemic, with HIV transmissible through blood products. About half of the hemophiliacs in the
United States contracted HIV and thousands died, according to the National Hemophilia Foundation. Although Mr. Price never contracted HIV, he did get hepatitis C through donated blood, which was later cured with treatments of interferon.
At 50, Mr. Price has outlived the other hemophiliacs in his family. A cousin in Texas died of AIDS. His uncle likely died of a brain hemorrhage. One of his grandmother’s brothers died as a toddler, and another committed suicide in his 20s.
When Mr. Price would go to his many doctors’ appointments and treatments over the years, he would always ask about new treatments on the horizon.
Scientists had been talking about the possibility of using gene therapy for hemophilia since the late 1990s, and while some experiments showed early promise in encouraging the body to produce factor VIII, the results weren’t durable. After a year or less, the body would go back to being unable to produce factor VIII, and bleeding episodes would resume.
Then, about five years ago, Mr. Price got a call from the Hemophilia Center of Western Pennsylvania asking if he wanted to be part of a new study. “They said, ‘If this works, you may possibly be cured.’ I said, ‘ What hospital and what time do I haveto be there?’ ”
Gene therapy works by using a virus to introduce new genetic material into the body that takes over existing genes. “You can think of the virus like a truck carrying cargo,” said Dr. Ragni. “It goes into a cell, puts a copy of itself into the nucleus and takes over the genetic material of the cell, which allows it to make factor VIII, and it goes into the blood stream.”
Gene therapy is under experimentation to help treat numerous genetic diseases, from sickle cell anemia to cystic fibrosis to forms of blindness.
Mr. Price expected that getting injected with genetic material would be a major procedure, and he packed expecting to stay the night at UPMC. Instead, he got the shot and was told he could leave after half an hour. He suffered no side effects whatsoever. And he hasn’t had to do a single infusion of factor VIII since.
“There were no negative results from the genetic stuff at all – It was all positive. How often does that happen?” he said. “They just put stuff in there that told my body, hey dummy, start making factor VIII. You’ve been slacking for 45 years now. [It’s] Time to pick up the pace.”
Most participants in the study were given steroids along with the gene therapy to reduce the chance of their bodies mounting an immune reaction to the genetic material. Two of the study subjects stopped making factor VIII, presumably because of an immune response. But the other 16 continued to produce factor VIII as long as they were followed by the study.
Dr. Ragni said that participants in the study averaged factor VIII levels at only 12 percent of what a non-hemophiliac would produce, but that amount was enough to virtually eliminate bleeding episodes. The lower level may have been what made the study more successful than previous ones, she said. The treatment is only available to hemophiliacs on an experimental basis for now, but Dr. Ragni hopes that it will go up for FDA approval in the next year or two.
For Mr. Price, it’s been absolutely life changing. He still can’t run any distance and still has lingering joint damage, but he has been able to play soccer with his sons, ages 7 and 10, and take them to Colonial Williamsburg and two trips to Disney World, spending entire days walking.
“One wanted to go hunting this year, so I took him deer hunting, and whenever we got bored sitting, we walked through the woods and talked,” he said. “I couldn’t have done that before. There’s no way – I would have had to drive my truck up to the field.”
The hardest part at times is convincing himself that it’s going to last.
“It’s been five years and I still feel like this is going to end, that I’ll wake up and my ankle will be exploded out and in pain,” he said. “But it hasn’t happened yet.”