Wednesday, August 11, 2010

Bone Marrow Stem Cells Offer Hope Against Devastating Skin Disease
Wednesday, August 11, 2010
By: Liz Szabo, USA Today

To anyone else, the prospect of putting a small child through a bone-marrow transplant might be terrifying. Theresa Liao -- mother of two children born with a rare, excruciatingly painful skin disease -- saw the risky procedures as her sons' only chance for a normal life.

Bone-marrow transplants, usually used to treat leukemia, are perhaps the most harrowing of all medical therapies. Doctors first flood patients with enough toxic chemotherapy to destroy their immune systems, leaving them incapable of fighting off even the slightest infection. Doctors then rebuild the immune system by transplanting donated stem cells.

If all goes well, donor cells replace a child's original, diseased cells, and they are cured.

But the transplants carry enormous risks. Sometimes, in spite of massive, poisonous doses of chemo, children reject the donated cells or develop other, potentially fatal complications.

Doctors at the University of Minnesota launched a bold experiment to try the procedure on children with severe forms of epidermolysis bullosa, or EB, an inherited condition in which children are born without a crucial protein that keeps their skin attached to their bodies.

Patients such as Liao's children, Nate and Jake — whose story has been chronicled by USA TODAY since 2007 — developed huge, painful blisters from a simple hug. Their fingers become so scarred that their hands turn into mittens. About 60% die by age 15, says Jakub Tolar, a University of Minnesota bone marrow transplant specialist treating the Liao children.

"For kids with EB, it's very unsafe to be alive," Tolar says.

In a study published in today's New England Journal of Medicine, Tolar and his colleagues tried to replace the children's defective cells with ones from healthy donor, giving them the potential to make the crucial protein.

At age 15 months, Nate Liao became the first patient, receiving donated stem cells from his healthy older brother, Julian. His brother's cells were a perfect match, and Nate had few complications.

But Julian, a carrier for Nate's disease, only makes half as much of the protein as other kids, says the University of Minnesota's John Wagner, another developer of the therapy. So while Nate's skin improved, he hasn't been cured.

Five-year-old Jake Liao received the next transplant. Doctors knew the procedure would be riskier for Jake, because they were unable to find a perfectly matched sibling donor. Although Jake's skin also improved, he developed severe complications, dying in November 2008, shortly before his 6th birthday.

Another girl died from the chemotherapy, even before getting the transplant.

Researchers persevered, transplanting donor cells into 9 more patients. All have survived. One, 8-year-old Keric Boyd of Missouri — has improved enough to jump on a trampoline, says his mother, Krista Boyd.

Hundreds of patients with EB are on a waiting list for the transplant, Wagner says. Most won't receive it, because few insurance companies will cover such an experimental therapy, which costs hundreds of thousands of dollars.

But Wagner remains hopeful.

While doctors have long been using stem cells from bone marrow to cure leukemia, this is the first time that doctors have shown that stem cells can build new skin, Wagner says. Although he's working to improve the therapy for children with EB, he also hopes his research will help scientists working on gene therapy and other stem cell research.

Wagner already has given Nate a "booster" infusion of stem cells from his brother. Because Nate's immune system is now identical to Julian's, he can safety receive an unlimited number of donations, Wagner says. About 11% of the cells in Nate's skin, in fact, came from his brother.

Today, Theresa Liao holds out hope that Nate will continue to improve.

But she says she remains devastated by the loss of Jake, with whom she lived in the hospital for the last seven months of his life. Her family moved to a new home after he died, unable to live in the house that reminded them so much of Jake.

While her other sons miss Jake, they're also "happy to have me back," Liao says. "I had been at the hospital 23 hours a day."

Although Liao says she would like to curl up in a ball, she forces herself to go on for the sake of her other children. It comforts her to think that Jake will never really be gone, she says, because he will live on through research that may help other families.

"Jake died at 9:11 a.m.," Liao says. "I would have been on the roof at 9:12 if I had a choice. But the kids need me. And when I see him again, I don't want him to be mad at me. I want him to be proud."

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