A chance for a better life
In his work as a pediatric oncologist, Jakub Tolar, M.D., Ph.D., sees tragedy every day. But little compares with the heartbreak he sees working with children who have epidermolysis bullosa (EB), a fatal disease that can cause the skin to slough off at even the slightest touch.
“This is one of the most awful diseases I’ve ever seen,” Tolar says.
Children with EB have a mutation of the collagen type 7 protein, which holds the skin together. And while missing patches of skin are one of the most outwardly apparent signs of the disease, they’re only part of the complex difficulties these children and their families face.
Collagen type 7 is found in other tissues in the body, as well, including the lining of the esophagus and thymus. With an esophagus full of lesions, it becomes painful to eat. And because of the body’s constant but flawed efforts to repair itself, fingers can fuse together.
Eventually, usually by age 20, these children will die of skin cancer.
But not if Tolar has his way. Though he is part of the pioneering University of Minnesota team offering experimental but risky blood and marrow transplants aimed at curing the disease, his latest research is focused on finding a safer treatment alternative.
That’s exactly what got Paul Joseph at the Epidermolysis Bullosa Medical Research Foundation and Alex Silver of the EB Research Partnership behind the project. Together the two foundations have contributed $450,000 to Tolar’s work—matching gifts from other donors dollar for dollar. The University’s Medical School and Department of Pediatrics each contributed generously to the match, and other donors pooled together to raise the last $250,000.
A safer transplant
One approach Tolar is taking to make treatment safer, which he calls “natural gene therapy,” would take advantage of healthy patches of skin that are present on some children with EB. A medical team would remove some of those healthy skin cells, turn them into powerful stem cells called induced pluripotent stem cells (or iPS cells, which can be coaxed into becoming any type of cell in the body), expand them in the lab, and give them back to the patient where they would grow more healthy skin.
Another approach, called “seamless gene therapy,” would involve removing some of the patient’s skin cells, “cutting” the DNA at the mutation to correct the gene in the lab, growing those corrected iPS cells into blood-forming or skin cells, and reintroducing them into the child’s body.
These experimental techniques should eliminate the rejection risk normally associated with transplants because patients are essentially receiving transplants of their own cells, Tolar says.
They also could help heal thermal or chemical burns and treat autoimmune diseases of the skin. And the same concept—modifying a patient’s own cells to mend or prevent damage—could be applied to help heal the heart after a heart attack or repair the pancreas of someone who has diabetes, he says.
Joseph and Silver have personal motivation for making sure this research prospers. Joseph’s 8-year-old son, Brandon, and Silver’s 4-year-old son, Jackson, both were born with EB.
Jackson was born with his skin intact. But when nurses removed the Band-Aid covering his post-birth heel prick, Jackson’s skin went with it. That skin has never fully healed.
Everyday life with EB can be complicated. At times, simple activities like walking and taking a bath can be agonizing because of constant open wounds. EB also can make nutrition a challenge. “Some days are hard, but Jackson’s indomitable spirit is an inspiration to everyone around him,” Silver says.
Brandon Joseph, who is now in grade school, is adjusting to the fact that he’s different from other kids who get to play sports on the weekend, his dad says.
“[Brandon] is a good reader and he’s a bright kid. He’s very inquisitive,” Paul Joseph says. And that means that he often has “big life questions”—why this is happening to him, why no one can make the EB go away—that are downright impossible for his parents to answer.
Expertise and enthusiasm
Joseph and Silver are hoping that, with a little help, they’re giving Tolar the resources to cure EB. They joined forces to raise awareness of this devastating disease from coast to coast—the Josephs live in California and the Silvers live in New York—and have inspired donors from the national community to support this effort through their dollar-for-dollar match. The goal? That no more children will have to ask those impossible questions, and no more parents will have to experience the heartbreak of having no answers.
As leaders of two organizations that seek high-quality research projects with the potential to make the biggest impact possible, Joseph and Silver have done their homework and know expertise when they see it.
“[Tolar] thinks outside the box, but he is also deeply grounded in science,” Silver says. “Jakub’s work is cutting-edge. It is in theory the holy grail because it’s both a personalized therapy and potential cure in one.”
Plus, Tolar is so genuine in the way he talks about his desire to find a safer treatment for kids with EB that it’s easy to rally behind him, adds Joseph.
“Jakub’s enthusiasm is very infectious,” Joseph says. “When you speak to him, you really get the feeling that he’s passionate and is going to see this through.”
With Tolar’s drive and the right financial support, Joseph and Silver are confident that this research will make a difference in the lives of children today who have EB and other related skin diseases. And maybe someday, Jackson and Brandon will be able to take off their shoes without worrying about taking off skin with them.
“The best gift we can give Jackson and any child with EB,” Silver says, “is a chance at having a good and pain-free life.”