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Incurable skin disease: doctors save the life of seven-year-olds with new gene therapy


Butterfly child gets a second skin through gene therapy

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

Skin peels off with the slightest touch

For the first time, doctors have successfully treated a boy with massive skin damage with gene therapy. The boy suffers from the life-threatening butterfly disease, in which the skin becomes detached from the slightest touch with great pain. In order to save the life of the child, 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 areas and thereby largely helped the boy complaint-free life, according to the report from the Bergmannsheil University Medical Center.

Skin layers are not sufficiently anchored to one another

The hereditary disease epidermolysis bullosa is considered incurable and severely limits the quality of life of those affected. It is also known 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 that are responsible for the formation of the laminin-332 protein. If these are not intact, the upper skin layer (epidermis) can only insufficiently bond with the underlying skin layer (dermis). As a result, even the slightest impact or impact causes blisters, wounds and scarring to form on the skin surface and the skin to become detached.

Boy weighs only 17 kilograms

Depending on the severity of the disease, it can also affect internal organs or cause severe functional disorders. It is often life-threatening - this also applies to little Hassan. When the then seven-year-old was admitted to the children's intensive care unit of the Catholic Clinic in Bochum in June 2015, 60 percent of his epidermis was already destroyed, reports the Bergmannsheil.

"He suffered from severe sepsis with a high fever and weighed only 17 kilograms - a life-threatening condition," said Dr. Tobias Rothoeft, senior physician at the University Clinic for Pediatric and Adolescent Medicine at the Catholic Clinic in Bochum.

Cooperation with Italian colleagues

Since all established therapies had failed, the team of pediatricians and plastic surgeons in Bochum opted for 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 gene therapy for epidermolysis bullosa on two patients - but only used smaller skin grafts.

After the parents had given their consent and the necessary permits had been obtained, the project could start. The German doctors sent some of the seven-year-old's skin cells to Modena. The Italian colleagues introduced the healthy gene into the resulting epidermal stem cells using so-called retroviral vectors. The genetically modified stem cells were then multiplied in the laboratory and processed into transgenic skin grafts.

Almost all body parts covered with bred

After certification of the surgical center of the Bergmannsheil University Clinic as a genetic engineering facility, the cultivated skin could be transplanted in three operations on the arms and legs, the entire back, the flanks and parts of the abdomen, as well as the neck and face.

"In total, the little patient was transplanted with 0.94 square meters of transgenic epidermis to cover all defects and thus 80 percent of his body surface," said private lecturer Dr. Tobias Hirsch, Senior Consultant at the Clinic for Plastic Surgery and Severe Burn Injuries at Bergmannsheil.

After a short time the child felt better, the changed stem cells had reportedly formed a new epidermis with intact laminin-332 protein in the area of ​​all transplanted skin areas. “After the second operation, his condition improved enormously. Today his skin is stable, he goes to school, plays football and can lead a largely normal life, ”Tobias Rothoeft from the children's clinic in Bochum told the news agency“ dpa ”.

The healing of injuries to the new skin was no different from that of other children. The introduction of the intact gene into the genetic material of the epidermal stem cells had therefore worked and could be proven to be stable by the scientists.

According to the international treatment team, the boy is the world's first patient to receive extensive skin grafts from transgenic epidermal stem cells, reports Bergmannsheil. "This approach offers considerable potential for the research and development of new therapeutic methods for the treatment of epidermolysis bullosa and of patients with severe skin damage," explains Dr. Tobias Hirsch.

Extreme challenge for the team of doctors

The therapy of little Hassan, however, demanded a lot from the experts: "Transplanting 80 percent of the skin and monitoring the patient intensively over eight months was an extreme challenge," emphasize Tobias Rothoeft and Tobias Hirsch. “The close cooperation between the Bochum clinics and the expertise of the University of Modena has led to success. We are very proud of this."

According to the experts, it must now be shown whether the course of therapy continues to be so positive. Because in general, gene therapies like this run the risk that the new gene will integrate into an unfavorable location in the genome and, in the worst case, lead to 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 received smaller skin grafts a few years ago. (No)

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