U team discovers 'powerhouse' new treatment in fight against deadly skin disease

Jonathan Pitre is a teenager who loves to write science fiction as an escape from the painful disease that causes his body to be coated with wounds.

But the breakthrough bone-marrow transplant he just received at the University of Minnesota is anything but fantasy.

A decade after performing the world's first bone marrow transplants to treat epidermolysis bullosa — a rare and potentially fatal skin disease — university researchers believe they have discovered a "powerhouse" new formula that advances their research, helps the body grow new skin and will allow patients such as Pitre, 17, to live longer, less painful lives.

"It's really not miraculous. It certainly isn't science fiction," said Dr. Jakub Tolar, director of the U's stem cell institute and the world leader in transplant therapies for EB. "It's based on the hard work of our predecessors. You accomplish something and then you use that knowledge to enhance the next step and the next step."

When they conducted the first transplants using donor bone marrow and umbilical cord blood in 2007, Tolar and colleagues were trying to produce a collagen that binds skin together and is lacking in EB patients. But they had little certainty about the types of cells that would work best.

Since then, research discoveries have allowed them to home in on mesenchymal stem cells, which they believe are uniquely good at bullying their way into the body and producing the missing collagen.

"This is the first time ever, that I know of, when you are infusing them with the goal that these cells will stay," Tolar said. "They will graft into the skin, set up shop there. It's as if these mesenchymal stem cells are coming home."

A transplant like Jonathan's occurs in a one-two punch. After receiving radiation and chemotherapy treatments to suppress the immune system, the patient receives an infusion of hematopoietic blood stem cells from a donor. Their job in this procedure is to give the patient a new immune system that won't reject the donor's mesenchymal cells when they are transplanted later.

Since the U received federal approval last fall to offer the treatment experimentally, seven patients have undergone the procedure.

Tolar said all seven are progressing — though Jonathan needed a second transplant this spring because the first one failed to knock out his old immune system.

Jonathan suffered an infection after his most recent transplant, which forced him to return to the hospital this month with high fevers and blisters on his face and mouth. Even so, Jonathan's mother, Tina Boileau, said she has been taking pictures since the latest transplant to document the progress for her son, whose back is covered with wounds but for a healthy spot on his right shoulder blade.

"They're actually in scabs," a sign of healing, said Boileau, who was the bone marrow donor for her son's transplant. "Which I've never seen before."

The desperation of children with the disorder and their families compelled the first transplants at the university in 2007. Even using the old approach, about two-thirds of patients saw improvements, but 10 of the first 30 recipients died from their diseases or complications of treatment.

The U's latest success with mesenchymal stem cells might end up being an incremental step. Earlier this year, Tolar and his colleagues published research showing success in an even more advanced therapy: laboratory testing using "gene editing" that can reprogram the patient's cells to produce healthy skin cells and tissue.

Further successes could lead to clinical trials in which a patient's own dysfunctional cells would be reprogrammed, preventing the need for chemotherapy and the replacement of their immune systems.

Before they came to the U, Boileau said, her son had run out of options. Managing his pain, once possible with over-the-counter Advil, had come to require opioid painkillers such as methadone. That made him groggy and complicated his already awkward life at school back home in Ottawa. Jonathan wasn't even able to eat lunch in the school cafeteria for fear of being accidentally bumped and suffering fresh wounds.

Then the Canadian government approved funding to make him his country's first recipient of an experimental bone marrow transplant for EB. And his home community rallied to support the family. Among other things, he has visited with pro hockey players from the Ottawa Senators, which also issued a contract adding him to their scout staff.

Inspired by the success of Christopher Paolini, who wrote the acclaimed Eragon science fiction novel as a teen, Jonathan has resolved to write his own science fiction book about a teen who develops the ability to overcome EB. The project resulted in long visits and e-mail exchanges between Tolar and his patient about medicine and physics, because Jonathan wants his story grounded in reality.

"They're almost soul mates," Boileau said.

Tolar said he enjoys the intellectual relationship and that his patient is providing an example of hope and teaching others about the disease: "He may be the only person [who] can bring this kind of view to others," Tolar said.

Centers across the world have learned from the U's transplant successes and have opened in Brazil, Chile and London, but none have performed as many transplants as the U. Tolar was recently interviewed by Polish television as part of an effort to raise funds for a child's transplant there.

Since they traveled from Ottawa last fall, Boileau and her son have mostly lived in the U's Masonic Children's Hospital or a nearby apartment — away from the rest of their family and Jonathan's beloved dog. Boileau said she remains optimistic because of her son's positive spirit amid so much pain and frustration.

Jeremy Olson • 612-673-7744