SALT LAKE CITY — Kids like Isaac have to grow up fast.
The 11-year-old, who is tall and gangly, spends most of his time zipping around the house or chasing after a soccer ball, stopping occasionally to sass his mom.
But for a few minutes every third day, Isaac stops dashing around long enough to sit down at the kitchen table and set up an IV full of protein to go into his arm — the only treatment for his rare blood clotting disorder called hemophilia.
“A little kid shouldn’t have to face mortality and pain on a daily basis,” said his mom, Danielle Nance. "You don't want that for your kid. But that's their reality."
She suffers from the same disease. As a young girl, she baffled many rural Utah doctors with painful bruises and cuts that never seemed to heal. Shortly after giving birth to Isaac, Nance became a hematologist herself to help advance hemophilia research.
That’s when she found that “there’s not a ton of research going on in rare disease in general.”
Now, Nance is asking for help.
The doctor and her son are part of a nationwide quest to persuade hemophiliacs to donate their DNA to a research database — the largest hemophilia genetic project in the world.
Hemophiliacs do not have a protein that helps with clotting, meaning that even minor injuries sometimes result in severe bleeding, joint damage and disability. The rare genetic disorder affects about 1 in 5,000 male births and is much rarer in females.
The goal of My Life, Our Future is to genotype 5,000 hemophiliacs and collect their data in one database.
“Hemophilia is a rare disease and we cant answer questions with a small number of patient samples,” said Barbara Konkle, a Seattle hematologist with Bloodworks Northwest, one of the founding partners of My Life, Our Future. The American Thrombosis and Hemostasis Network, the National Hemophilia Foundation and Biogen are the other founding partners.
“We can answer a few questions, but to really understand it and to move the area forward, we need to really pool clinical information and genetic information from a lot of people,” Konkle said.
Therapies like the one that Isaac does every three days — a dose of clotting protein delivered to the veins through a self-administered IV — represent “incredible advances” in hemophilia, Konkle said.
Still, there are limitations to how well this treatment works.
Researchers from the Centers for Disease Control and Prevention and the U.S. Hemophilia Treatment Center Network followed nearly 8,000 men with hemophilia for 13 years to see how advances in treatment had affected them. They published the somewhat surprising results earlier this month.
Even among the youngest cohort, one-third of patients reported frequent bleeds (more than five bleeds in six months) even though they had access to the most advanced therapies for much of their lives. One in 4 men also reported joint problems.
And the gap between men with severe hemophilia and mild hemophilia had not narrowed. Those with severe hemophilia continued to report three times the likelihood of activity limitations and twice the likelihood of needing a cane or wheelchair.
“I think we sort of thought we were going to avoid that with regular treatment,” Nance said. “It looks like we haven’t.”
Questions remain: Why do some people have more severe bleeding than others, even if they have the same levels of clotting factors?
Why do patients continue to underutilize their medication, despite doctors’ best efforts?
And why do up to a third of patients with severe hemophilia develop an immune reaction to the treatment, rendering it ineffective?
“There are big questions we need to figure out, and we need to understand why they’re happening,” Nance said. “(The treatments are) not working as well as we thought they would.”
For one, the IV infusion is not only cumbersome, it’s expensive. It's not uncommon for a hemophiliac’s medication to reach $500,000 to $1 million a year, according to Utah Hemophilia Foundation Director Scott Muir.
And second, the daily infusion is often painful and traumatic for young kids.
The foundation, which serves about 400 families in Utah, runs an annual camp where children learn to give themselves infusions: Find the vein. Angle the needle. Then push.
They start at the age of 8.
Many children with hemophilia learn to be cautious with the sports or activities they choose, said Muir. What they choose to do for a living is usually dictated by the expense of their treatments. Where they choose to live is usually limited by whether they can get their medication delivered there.
"That's a very difficult thing to tell young people who are looking at their future,“ Muir said. “But by the same token, part of what we do as a foundation is making sure that individuals understand that there are financial realities, but also making sure that they're strong self-advocates.”
Still, things are changing, especially with advancements in genetic sequencing, Muir said.
Nance knows about the benefit of genetic research, having taken a part in a study in California when she was newly married and contemplating children.
"Having that genetic information, knowing that it wasn't a 100 percent risk — it was a 50 percent risk with each pregnancy — those things were very helpful in choosing to go forward with the pregnancy," Nance said. "It took a level of uncertainty out of the equation."
The study "gave me power over my disease," she said.
Nance and her son both donated DNA to My Life, Our Future. They are now helping the program spread the word about the quest to collect 5,000 samples.
Since the project launched in 2012, nearly 3,900 people with hemophilia have volunteered to have their DNA sequenced and donated.
People who want to donate will go through the same process Nance and Isaac did: First, they need to get their blood drawn at their local hemophilia treatment center. My Life, Our Future will then arrange to extract the DNA and sequence the genes related to hemophilia, free of charge.
Patients will receive their personalized results, which they can choose to donate to the database for use by researchers. Any genetic data is scrubbed of identifying information.
Once Konkle and the other organizers collect enough samples, they will open the database to researchers.
The project has already identified several new mutations responsible for hemophilia, according to Konkle. She added that the project also has broader implications for treating heart attacks and other clotting complications.
“There have been incredible advances in hemophilia,” Konkle said. “We just want to see what more we could do.”
Nance's hope is that the database leads to new treatments for Isaac, who has been learning to do his own IV infusions since he was 8.
For him, it’s hard to see what the big deal is or even why needles might be considered scary.
He plays soccer. He can sprint a mile in 6 minutes flat. He wants to be a scientist or inventor, hopefully of hover cars.
“I’m way past ‘scary,’” Isaac declares. “I just do it and I’m like, ‘Bye, mom!’ And I go outside.”
For Nance, who grew up in an era when having hemophilia was much scarier, Isaac is "extraordinarily blessed" to be able to benefit from decades of research before his time.
Now, it's their turn to give back.
"I want better treatments for him and his peers and the new babies that are coming up," Nance said. "We're hoping to continue the momentum so we can get those last few samples."