Two years ago, doctors at the University of Minnesota took an enormous risk by putting a little boy with a terrible skin disease through a bone marrow transplant. For that boy, Nate Liao, it worked out, and he is healthier now.
Thursday, in a study published in the New England Journal of Medicine, the researchers are for the first time making public their results treating seven other children with the same genetic disease. In it, they acknowledge just how risky the procedure is: Two of the seven, including the older brother of the first patient, died as a result of the treatment.
But in the others it worked -- a leap forward for a devastating and painful genetic disease for which there is no other treatment and a potentially significant advance for the use of adult stem cells.
"This is amazing," said Krista Boyd of Missouri, whose 8-year-old son was one of the five children who improved. "This is a transformation." More important, in a finding that even they found surprising, the researchers were able to show that cells from donated bone marrow somehow became healthy skin cells. That provides "cautious hope" that therapies for some 400 genetic skin disorders may be on the horizon, according to an accompanying editorial.
"It's paradigm-shifting," said Dr. John Wagner, the bone-marrow-transplant specialist who led the research.
At this point, however, he and his co-author, Dr. Jakub Tolar, don't know which -- or how many -- of the 30 to 50 different kinds of bone marrow cells are doing the job. That bone marrow worked at all was a surprise discovery they made while testing many different kinds of cells in mice genetically engineered to have the skin disease.
"Do we actually know how this works?" Tolar said. "No, we don't."
The disease, epidermolysis bullosa (EB), occurs in two to four out of 100,000 children. They lack the gene that creates a certain kind of collagen, and as a result their skin and the lining of their throats can tear and blister at the slightest bump or scrape. In the most severe cases, babies are born without skin on parts of their bodies and spend their lives with open sores and wrapped in protective bandages. Those who live to young adulthood usually die from an aggressive form of skin cancer.
Since the first transplant two years ago, Wagner has made the university something of a mecca for affected families, and hundreds of parents have called the U seeking information.
To date, however, because the treatment is experimental and is monitored by the Food and Drug Administration, only 12 children overall have received a transplant.
"It's abysmal to have to say we can't," said Tolar.
The results, published Wednesday, could accelerate broader use of the treatment and attract funding, the researchers said.
A desperate mom
It was Nate Liao's mother who inspired Wagner to consider a bone marrow transplant for EB patients in the first place. Desperate to find some relief for her sons, she challenged him to study adult stem cells as a treatment for the disease. After finding that the bone marrow transplant worked in mice, Wagner agreed to take her youngest son, now 4, as the first patient. The treatment didn't rid him of the disease, but today he needs fewer bandages, heals faster and can eat Doritos without damage to his throat, she said.
She knew the transplant would be more difficult for her older son, Jake, because his disease was more advanced and because the procedure is easier on younger children. It involves destroying the patient's own bone marrow and immune system with chemotherapy, and then replacing it with either donor bone marrow or umbilical cord blood.
The process is even more difficult in children with EB because of their fragile skin and their greater risk of infection.
Jake's body wouldn't accept the first transplant and after the second, he died in his mother's arms from infections.
"Nobody wants to be the first," Theresa Liao said of her wrenching decision. "Nobody wants to risk their child. But I made a promise to him when he was born, that we were going to go down swinging."
She misses him terribly, she said, and knows that many will question her choice. But those people, she said, do not understand the horror of EB -- as when a toddler rubs his eye and the eyelid peels off.
"I know where door number one leads," she said. "I'll try door number two."
Ethical issues
The ethical balance in such research is delicate, especially when it affects children, said Dr. Rick Kodish, a bioethicist at the Cleveland Clinic and a pediatric oncologist. But this case passes the litmus test because it's clear that despite the risk, the children stand to benefit from the treatment, he said.
"For too long in medicine and ethics we have been focused on the quantity of life and paid insufficient attention to quality," he said. "More importantly, future children will benefit."
For Keric Boyd, the transplant was harrowing, said his mother. He went into respiratory failure and his kidneys shut down. But within a month, they could see the change in his skin. They hoped it wasn't their imagination, she said. Then one day as they walked down a hallway, she noticed him clapping his hands over and over.
She asked why.
"He said, 'I never could hear me clap before,'" she said. Now she doesn't leap to bandage him when he stumbles. He can ride a bike, wrestle with his older brother and jump on a trampoline. "We let him try anything he wants to try," she said.
Wagner and Tolar are now trying other combinations of cells to see if they can improve the outcome. They said they think that more than one cell is critical to the process and that somehow they home in to the damaged skin, where they make collagen.
They are also beginning to teach doctors at transplant centers in Europe and Canada how to do the procedure. At first they were reluctant to teach it because the patients presented such difficult problems. But, Wagner said, doctors in Europe persuaded him that it was unethical to restrict the treatment to only American children.
Josephine Marcotty • 612-673-7394