Incurable Skin Disease Physicians rescue seven-year-olds with new gene therapy life

Butterfly kid gets a second skin by gene therapy

Seven-year-old Hassan suffers from the so-called butterfly disease, a congenital skin disorder that has already destroyed much of the epidermis in the child. After all the established therapies had failed, a medical team launched a last attempt to save the boy's life through gene therapy. With great success, because only two years later, Hassan can again largely participate in the normal daily life. The researchers are currently reporting on the course of treatment in the journal "Nature".

Skin dissolves at the slightest touch

Physicians have successfully treated a boy with massive skin damage with gene therapy for the first time. The boy suffers from the life-threatening butterfly disease, in which the skin peels off as a result of the slightest touch in great pain. In order to save the child's life, the treatment team of the Ruhr University Bochum and the Center for Regenerative Medicine of the University of Modena (Italy) carried out an experimental therapy: They transplanted skin from genetically modified stem cells onto the wound surfaces and thereby largely helped the boy Complaint-free life, according to the statement of the Berufsgenossenschaftliche Universitätsklinikum Bergmannsheil.

Physicians transplanted a square foot of transgenic epidermis to a terminally ill boy. (Image: Alexander Raths / fotolia.com)

Skin layers are not sufficiently anchored to each other

The hereditary disease Epidermolysis Bullosa is considered incurable and severely limits the quality of life of those affected. It is also referred to as a "butterfly disease" because the skin - like the delicate wings of a butterfly - is extremely vulnerable.

This is due to mutations in certain genes responsible for the formation of the protein laminin-332. If these are not intact, the upper skin layer (epidermis) can not adequately connect with the underlying skin layer (dermis). As a result, even the slightest impact or impact causes bubbles, wounds and scarring to form on the surface of the skin and the skin peels off.

Boy weighs only 17 kilograms

Depending on how severe the disease is, it can also affect internal organs or cause severe dysfunction. Often it runs perilous - as in the case of little Hassan. When the then seven-year-old was admitted to the children's intensive care unit of the Catholic Hospital in Bochum in June 2015, 60 percent of his epidermis had already been destroyed, reports Bergmannsheil.

"He suffered from severe sepsis with a high fever and weighed only 17 kilograms - a life-threatening condition," Dr. Tobias Rothoeft, Senior Physician at the Department of Pediatric and Adolescent Medicine at the Catholic Hospital Bochum.

Cooperation with Italian colleagues

Since all established therapies had failed, the Bochum team of paediatricians and plastic surgeons decided in favor of an experimental therapy in view of the poor prognosis: the transplantation of genetically modified epidermal stem cells. The work of Prof. dr. Michele De Luca from the Center for Regenerative Medicine at the University of Modena (Italy). He had already tested a gene therapy for Epidermolysis Bullosa on two patients - but only used smaller skin grafts.

After the parents had agreed and the necessary permits were obtained, the project could start. The German doctors sent some skin cells of the seven-year-old to Modena. The Italian colleagues inject the healthy gene into the resulting epidermal stem cells with the aid of so-called retroviral vectors. Subsequently, the gene-modified stem cells were propagated in the laboratory and processed into transgenic skin grafts.

Almost all body parts covered with bred

After the certification of the surgical center of the Bergmannsheil University Hospital as a genetic engineering facility, the bred skin was transplanted into three operations on the arms and legs, the entire back, the flanks and parts of the abdomen as well as the neck and face.

"Overall, the small patient was transplanted 0.94 square meters of transgenic epidermis to cover all defects and thus 80 percent of his body surface," said Privatdozent Dr. med. Tobias Hirsch, Senior Consultant at the Department of Plastic Surgery and Heavy Burned Persons at Bergmannsheil.

After only a short time, the child was better, the altered stem cells had been reported to have formed a new epidermis with intact laminin 332 protein in the area of ​​all transplanted skin areas. "After the second surgery, his condition improved enormously. Today, his skin is stable, he goes to school, plays football and can lead a largely normal life, "said Tobias Rothoeft of the Children's Hospital in Bochum, told the news agency" dpa ".

In case of injuries to the new skin, the healing was no different than other children. The introduction of the intact gene into the genome of the epidermal stem cells had thus worked and could be proven by the scientists as stable.

The large area skin transplantation was a great challenge for the doctors. (Image: AntonioDiaz / fotolia.com)

According to the international treatment team, the boy is the first patient in the world to receive skin transplants from transgenic epidermal stem cells on a large scale, Bergmannsheil reports. "This approach offers significant potential for researching and developing new therapies for the treatment of epidermolysis bullosa and patients with major skin damage," explains Dr. Tobias deer.

Extreme challenge for the medical team

However, the therapy of little Hassan demanded something from the experts: "To transplant 80 percent of the skin and to monitor the patient intensively over eight months was an extreme challenge," emphasize Tobias Rothoeft and Tobias Hirsch. "The close cooperation between the Bochum hospitals and the expertise of the University of Modena has led to success. We are very proud of this."

Whether the course of therapy continues to be so positive, according to the experts, must now show. In general, gene therapies like this one run the risk of the new gene integrating in an unfavorable place in the genetic material and, in the worst case, of developing a cancer. So far, no such developments or a tumor have been discovered in the boy, the researchers inform. The same applies to the two patients who had already received smaller skin grafts a few years ago. (No)