Minnesota scientist pioneers EB treatment
Jonathan Pitre’s chance for a lesspainful life is due to a Czech-born scientist who couldn’t turn away a desperate mother 10 years ago.
Dr. Jakub Tolar, a Minnesota pediatric transplant specialist, was approached by a woman with two children, both of whom suffered from epidermolysis bullosa (EB). She had read about his work with stem cells, and wondered if he would consider using the approach to treat EB.
“This was not my idea. The only credit we can take is that we did not send her away,” says Tolar, director of the University of Minnesota’s Stem Cell Institute.
Until then, Tolar had never worked on skin. His research had concentrated on using stem-cell transplants to treat childhood cancers and rare, inherited disorders, such as Hurler syndrome. But he didn’t dismiss the woman’s idea.
“We were receptive. We said, ‘This may be crazy, but it may be good crazy,’ ” remembers Tolar. “The fact is that the more I know about these things, the more I’m painfully aware how little I know.”
There are hundreds of rare, genetic diseases that have no cure. But Tolar decided to invest time and energy in EB, a devastating and often fatal skin disease, because he recognized few others would take the same risk.
He studied skin physiology, and its complex web of cellular interactions, and he found an opportunity.
“What I realized, to my amazement, is that bone-marrow stem cells, which I know well, are very similar to the ones in skin.”
Tolar believed it might be possible to use stem cells from one part of the body — the bone marrow — to heal another: the skin.
Bone marrow contains multipurpose stem cells along with those that produce most of the body’s blood cells. Tolar knew cells from the bone marrow migrate to the site of an injury, and he theorized that a stem-cell transplant might offer EB patients a “systemic” approach to skin healing by manufacturing the key protein that their bodies lack.
He engineered a mouse model to test the theory, and after more than a year of failure, it worked. Tolar proved that a bone-marrow transplant could give mice genetically incapable of producing type VII collagen the power to do just that.
“It was eureka. It was phenomenal,” he says.
That breakthrough offered the scientific basis for a human clinical trial, launched in October 2006. At the time, neither Tolar nor anyone else knew whether patients with severe EB could survive the demanding treatment. Already at risk for infection because of their open wounds, the EB patients would need to have their immune systems suppressed to receive a transplant.
Parents, however, were desperate for options. Living with severe EB is intensely difficult, and few with the disease survive beyond their 20s.
Tolar’s initial clinical trial proved that in five of six patients, the stem-cell transplant resulted in a measurable improvement in collagen production. Some patients experienced dramatic benefits: reduced blistering, tougher skin, better wound healing.
But the transplant is high-risk. In the decade since he pioneered the treatment, Tolar has had 30 children in his clinical trial. Eight have died, most from infections.
Still, it is the only meaningful treatment for severe EB sufferers such as Ottawa’s Jonathan Pitre.