“I just try to get through it, the best you can, no matter how much it hurts...” - Ileana Peralta
It wasn’t until Ileana Peralta was in junior high school that she summoned the courage to Google her own disease. The teenager from Livermore knew almost everything about her inherited condition, Epidermolysis bullosa, a tongue twister even doctors call just EB. The disease is caused by the lack of the collagen gene that makes the glue that tethers layers of skin together. It makes her skin seem as fragile as a butterfly’s wing.
Ileana and other children with EB go through life with much of their bodies wrapped in gauze, like a burn patient. Their skin, at the slightest trauma, is prone to form blisters, which are vulnerable to infection. Scarring eventually curls fingers and toes, fusing them. To varying degrees, these children are condemned to a life of pain and disfigurement.
EB is rare. Ileana’s severe form of it, called recessive dystrophic, affects between one and four per one million in the United States, said Dr. Alfred T. Lane, a pediatric dermatologist. Dr. Lane was recruited to Stanford University Medical School 19 years ago to search for treatments for EB, and has been working on it ever since.
“It’s the worst skin disease that I know of,” he said. “This disease just cries out for help.”
The handful of doctors in the United States who deal with EB are experimenting with some of the most advanced technologies in medicine — gene therapy, stem cell therapy and bone marrow transplantation — as a means of eventual treatment.
Last fall, the California Institute of Regenerative Medicine, the state agency that runs the voter-approved $3 billion stem cell research program, allotted $11.7 million to Stanford to find a way to harness the newest stem cell technologies against EB. The goal is a clinical trial by 2014.
Under Dr. Lane’s direction, the California stem cell money will pay for an approach using new techniques that transform ordinary skin cells into all-purpose stem cells. In theory, these stem cells can be engineered to carry the missing collagen gene, and can then be coaxed to grow large amounts of healthy skin grafts, immunologically compatible with each patient, like Ileana.
When Ileana trolled the Web for information about her disease, she discovered that children who have it may not survive to adulthood. “The part that scares me is that some kids died from it,” she said. “I’m glad I’m still here.”
For most of Ileana’s life, Dr. Lane’s team has focused on developing gene therapy. The idea is to implant the missing gene — for a protein called collagen VII — in skin grafts. The chainlike collagen proteins, absent or damaged in people with EB, anchor the top layer of skin to the underlying dermis.
Engineered viruses would ferry the missing gene to laboratory cultures of the patient’s skin, to be grown in sheets and later grafted. A clinical trial among adult patients is pending.
The latest technique, sometimes called reprogramming, holds the promise of sidestepping the troublesome issues surrounding the use of embryonic stem cells — controversial because they are derived from human embryos that are destroyed a few days after fertilization.
Reprogramming seemed like science fiction until 2006, when Dr. Shinya Yamanaka proved it could be done in mice. In 2007, Dr. Yamanaka and other researchers showed it could be done with human cells.
Reprogrammed cells are currently too dangerous for use in human studies, and a variety of hurdles must be cleared before such studies can happen. One study recently found, for example, that reprogrammed cells have a more limited lifespan than stem cells derived from embryos.
On the other hand, researchers are rapidly fine-tuning the mechanisms of cellular reprogramming, making it simpler, more efficient and better understood. The field is now among the hottest in molecular biology.
More controversial is an entirely different approach using bone marrow transplants, which swap a patient’s own marrow with those of a healthy donor. The idea is to treat EB as a disease of the whole body, rather than one that can be repaired with skin grafts. EB affects not only the skin, but also weakens mucosal tissues in the mouth and gut, which cannot be grafted.
Dr. John E. Wagner Jr., a pediatric cancer researcher at the University of Minnesota Medical School, has done bone marrow transplants on seven EB children after studies on mice that showed that a select group of bone marrow cells could migrate to the skin and, for reasons not fully understood, replace missing collagen.
Four of those patients “are having improved quality of life,” said Dr. Wagner, who has yet to publish his pediatric results. But two of the children died — one from infections five months after an initial transplant, and the other during chemotherapy, before healthy bone marrow from a donor could be transplanted.
Dr. Wagner agonizes over those deaths, but is convinced that the disease was so severe that it warranted the risk.
“I normally take care of patients with leukemia,” he said, “but then I think there are some things worse than leukemia.”
Dr. Wagner’s work is backed by DebRA, the Dystrophic Epidermolysis Bullosa Research Association of America, as well as the Epidermolysis Bullosa Medical Research Foundation, two charitable organizations founded by parents.
Dr. Lane of Stanford has reservations about the bone marrow procedure. “For a child with large wounds,” he said, “you are really setting them up for infection.”
Dr. Arthur Caplan, a bioethicist at the University of Pennsylvania, is also uneasy about conducting risky procedures on children.
“The sicker the children become, the harder it is to secure good, informed consent,” Dr. Caplan said. “In my experience, parents become desperate. They want to have hope, and often researchers want to offer hope.”
For her part, Ileana said she was in no hurry to be a guinea pig. “I probably want to wait until they know what they are doing,” she said.
Now 15 and a freshman at Grenada High in Livermore, Ileana confronts her disease with a combination of pluck and a straightforward attitude befitting someone considerably older. She is as matter-of-fact about everyday life as she is about her disease. She confesses to struggling in math at school and far prefers drawing. Her sketchbook is full of cartoon bats and characters like Jack Skellington from “The Nightmare Before Christmas” and SpongeBob SquarePants.
Ileana knows the sting of EB every day when her mother, Stephanie Peralta, bathes her and wraps her in gauze. It can take 45 minutes to whirl the yards of white cotton bandage around her arms, her legs and her stomach. Some days the sores hurt more than others. Some days they hardly bother her at all.
Bandaging Ileana is a labor of love for Ms. Peralta, a 31-year-old single mother, who lost her job at a freight forwarding company when the recession hit. She was 16 when she became pregnant with Ileana. Doctors knew when Ileana was born that something was wrong: on her right leg, there was no skin from the knee down.
“I was a teenage mom with a sick child,” Ms. Peralta said. “I grew up in a hurry, and just dealt with it.”
Ileana appears to have inherited her mother’s strength. “I just try to get through it, the best you can, no matter how much it hurts,” she said.
When she goes outside, she knows people sometimes stare. “If they’re curious, they’ll ask,” she said. “It’s O.K. to ask.”
Recently she attended a party, and met a girl whose mother has cancer. “I asked her about it,” she said. “Pretty soon we were swapping stories.”