Doctors used genetically modified stem cells to "grow" skin for a child with epidermolysis bullosa
The rare genetic skin disease had damaged 80% of his skin
For the first time, doctors were able to treat a child who had a life-threatening rare genetic skin disease through a transplant of skin grown using genetically modified stem cells.
The grafts replaced 80% of the boy’s skin.
The skin of his arms, legs, back and flanks, and some of the skin on his stomach, neck and face was missing or severely affected due to epidermolysis bullosa.
The compassionate-use experimental treatment is detailed in a case study published in the journal Nature on Wednesday.
Skin as fragile as a butterfly’s wings – that’s how children with epidermolysis bullosa are described and why they’re often called butterfly children.
The disease, of which there are five major types and at least 31 subtypes, is incurable. People with the condition have a defect in the protein-forming genes necessary for skin regeneration.
About 500,000 people worldwide are affected by forms of the disease. More than 40% of patients die before reaching adolescence.
Their skin can blister and erode due to something as simple as bumping into something or even the light friction of clothing, according to an email from Dr. Jouni Uitto, a professor and chairman of the Department of Dermatology and Cutaneous Biology at the Sidney Kimmel Medical College in Philadelphia. Uitto was not involved with this study.
Epidermolysis bullosa makes the skin incredibly susceptible to infections, and in the case of 7-year-old Hassan, whose treatment was detailed in Nature, those infections can be life-threatening.
A week after he was born in Syria, Hassan had a blister on his back, his father said through an interpreter in an interview provided by the hospital in Germany where the boy was treated.
Hassan’s last name, as well as the first names of his family members, are not being disclosed to protect the privacy of the family.
In his first few weeks of life, Hassan was immediately diagnosed with epidermolysis bullosa, and their doctor in Syria told Hassan’s family that there was no cure or therapy.
Over the years, their efforts to find help for their son’s disease led the family to the Muenster University hospital in Germany in 2015, when Hassan was 7. His condition worsened, and he struggled with severe sepsis and a high fever. He weighed just over 37 pounds.
They didn’t think he would make it, and doctors at Muenster decided in summer 2015 to transfer Hassan to the Ruhr-Universität Bochum’s University Hospitals, including the burn center – one of the oldest in the country.
The search for treatment
By the time Hassan arrived at Bochum, he had lost two-thirds of his surface skin.
“We had a lot of problems in first days just keeping him alive,” said Dr. Tobias Rothoeft, consultant at the University Children’s Hospital at Katholisches Klinikum Bochum.
Doctors tried to promote healing by changing his dressings and treating him with antibiotics, as well as putting him on an aggressive nutrition schedule, but nothing helped. They even tried transplanting skin from Hassan’s father.
“By that time, he had lost 60% of his epidermis, the upper skin layer, and had 60% open wounds all over his body,” said Dr. Maximilian Kueckelhaus of the Department of Plastic Surgery at Bochum’s Burn Center.
Every approach failed, so the doctors prepared Hassan’s family for what end-of-life care would entail. But the parents pleaded, asking the doctors to consult studies and research for experimental treatments that might help.
They found Dr. Michele De Luca at the University of Modena’s Center for Regenerative Medicine in Italy. His publications described an experimental treatment transplanting genetically modified epidermal stem cells that healed small, non-life-threatening wounds in adults.
The medical team reached out to De Luca, asking whether he could help them replicate the procedure on a larger scale to help Hassan, and he agreed. De Luca told Hassan’s parents that he believed there was a 50% chance of the treatment being successful.
They were more than willing to accept the risk, to do anything to help their son have a chance at a normal life.
Hassan “was in severe pain and was asking a lot of questions: ‘Why do I suffer from this disease? Why do I have to live this life? All children can run around and play. Why am I not allowed to play soccer?’ I couldn’t answer these questions,” his father said. “It was a tough decision for us, but we wanted to try for Hassan.”
Growing sheets of skin
To obtain the skin’s stem cells, the doctors took a small biopsy – only accounting for 1½ square inches – from an unaffected part of Hassan’s skin. The stem cells were processed by De Luca in Italy. A healthy version of the gene that is normally defective in epidermolysis bullosa patients was added to the cells, along with retroviral vectors: virus particles that assist the gene transfer.
This genetic transfer would essentially “correct” the cells.
The single cells were grown and cultivated on plastic and fibrin substrate, which is used to treat large skin burns, to form a large piece of epidermis. This method enabled the researchers to grow as much skin as they needed. The whole process took three to four weeks, Kueckelhaus said.
Once the sheets were ready, they were transferred from Italy to Germany and transplanted onto the well-cleaned wounds right away during two surgeries. The first procedure in October 2015 applied the sheets to Hassan’s arms and legs. The second surgery, in November, grafted the sheets to Hassan’s entire back and the other affected areas.