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Transplantation of transgenic epidermal cultures successfully created a new, functional epidermis for a boy suffering from junctional epidermolysis bullosa.

Junctional epidermolysis bullosa is a genetic disease characterized by chronic skin wounds, blisters, and erosions. The chronic wounds not only increase a patient’s risk of skin cancer, they also can cause itching, pain, limited mobility, and poor quality of life, wrote Tobias Hirsch, MD, of BG University Hospital Bergmannsheil, Bochum, Germany, and colleagues (Nature. 2017. doi: 10.1038/nature24487). There is no cure for the disease, and more than 40% of patients die prior to adolescence.

Previous studies have shown that epidermal stem cells can be used to repair a damaged epidermis, they noted. However, the technique has been criticized for being insufficient to treat the large lesions common to this disease.

The researchers described the case of a 7-year-old boy who was admitted to a children’s hospital in Germany in June 2015 with junctional epidermolysis bullosa so severe that approximately 80% of his total body surface area was affected. The patient had a genetic mutation that had resulted in blisters on much of his body since birth. Approximately 6 weeks prior to his hospital admission, he developed Staphylococcus aureus and Pseudomonas aeruginosa infections that worsened his condition. After other treatments failed, the patient’s parents consented to a combination of ex vivo cell and gene therapy, in which cultures taken from a biopsy of uninvolved skin were used to develop transgenic epidermal grafts. The grafts were applied sequentially on a dermal wound bed.

“Virtually complete epidermal regeneration was observed after 1 month,” Dr. Hirsch and associates wrote. Over 21 months, the regenerated epidermis healed and remained stable even when subjected to mechanical stress.

For follow-up, the researchers reported on 10 punch biopsies taken at 4, 8, and 21 months after the grafting procedure. “The epidermis had normal morphology and we could not detect blisters, erosions, or epidermal detachment from the underlying dermis,” they noted.

The patient has remained stable since being discharged from the hospital in February 2016, and requires no ointment or medications to maintain a healthy epidermis, they said.

“This approach would be optimal for newly diagnosed patients early in their childhood,” Dr. Hirsch and associates noted. “A bank of transduced epidermal stem cells taken at birth could be used to treat skin lesions while they develop, thus preventing, rather than restoring, the devastating clinical manifestation that arise in these patients.

The study was supported in part by several government grants from organizations including the Italian Ministry of Education and the European Research. Two of the researchers are cofounders and members of the Board of Directors of Holostem Terapie Avanzate, which met all costs of good manufacturing practice production and procedures of transgenic epidermal grafts.

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Transplantation of transgenic epidermal cultures successfully created a new, functional epidermis for a boy suffering from junctional epidermolysis bullosa.

Junctional epidermolysis bullosa is a genetic disease characterized by chronic skin wounds, blisters, and erosions. The chronic wounds not only increase a patient’s risk of skin cancer, they also can cause itching, pain, limited mobility, and poor quality of life, wrote Tobias Hirsch, MD, of BG University Hospital Bergmannsheil, Bochum, Germany, and colleagues (Nature. 2017. doi: 10.1038/nature24487). There is no cure for the disease, and more than 40% of patients die prior to adolescence.

Previous studies have shown that epidermal stem cells can be used to repair a damaged epidermis, they noted. However, the technique has been criticized for being insufficient to treat the large lesions common to this disease.

The researchers described the case of a 7-year-old boy who was admitted to a children’s hospital in Germany in June 2015 with junctional epidermolysis bullosa so severe that approximately 80% of his total body surface area was affected. The patient had a genetic mutation that had resulted in blisters on much of his body since birth. Approximately 6 weeks prior to his hospital admission, he developed Staphylococcus aureus and Pseudomonas aeruginosa infections that worsened his condition. After other treatments failed, the patient’s parents consented to a combination of ex vivo cell and gene therapy, in which cultures taken from a biopsy of uninvolved skin were used to develop transgenic epidermal grafts. The grafts were applied sequentially on a dermal wound bed.

“Virtually complete epidermal regeneration was observed after 1 month,” Dr. Hirsch and associates wrote. Over 21 months, the regenerated epidermis healed and remained stable even when subjected to mechanical stress.

For follow-up, the researchers reported on 10 punch biopsies taken at 4, 8, and 21 months after the grafting procedure. “The epidermis had normal morphology and we could not detect blisters, erosions, or epidermal detachment from the underlying dermis,” they noted.

The patient has remained stable since being discharged from the hospital in February 2016, and requires no ointment or medications to maintain a healthy epidermis, they said.

“This approach would be optimal for newly diagnosed patients early in their childhood,” Dr. Hirsch and associates noted. “A bank of transduced epidermal stem cells taken at birth could be used to treat skin lesions while they develop, thus preventing, rather than restoring, the devastating clinical manifestation that arise in these patients.

The study was supported in part by several government grants from organizations including the Italian Ministry of Education and the European Research. Two of the researchers are cofounders and members of the Board of Directors of Holostem Terapie Avanzate, which met all costs of good manufacturing practice production and procedures of transgenic epidermal grafts.

 

Transplantation of transgenic epidermal cultures successfully created a new, functional epidermis for a boy suffering from junctional epidermolysis bullosa.

Junctional epidermolysis bullosa is a genetic disease characterized by chronic skin wounds, blisters, and erosions. The chronic wounds not only increase a patient’s risk of skin cancer, they also can cause itching, pain, limited mobility, and poor quality of life, wrote Tobias Hirsch, MD, of BG University Hospital Bergmannsheil, Bochum, Germany, and colleagues (Nature. 2017. doi: 10.1038/nature24487). There is no cure for the disease, and more than 40% of patients die prior to adolescence.

Previous studies have shown that epidermal stem cells can be used to repair a damaged epidermis, they noted. However, the technique has been criticized for being insufficient to treat the large lesions common to this disease.

The researchers described the case of a 7-year-old boy who was admitted to a children’s hospital in Germany in June 2015 with junctional epidermolysis bullosa so severe that approximately 80% of his total body surface area was affected. The patient had a genetic mutation that had resulted in blisters on much of his body since birth. Approximately 6 weeks prior to his hospital admission, he developed Staphylococcus aureus and Pseudomonas aeruginosa infections that worsened his condition. After other treatments failed, the patient’s parents consented to a combination of ex vivo cell and gene therapy, in which cultures taken from a biopsy of uninvolved skin were used to develop transgenic epidermal grafts. The grafts were applied sequentially on a dermal wound bed.

“Virtually complete epidermal regeneration was observed after 1 month,” Dr. Hirsch and associates wrote. Over 21 months, the regenerated epidermis healed and remained stable even when subjected to mechanical stress.

For follow-up, the researchers reported on 10 punch biopsies taken at 4, 8, and 21 months after the grafting procedure. “The epidermis had normal morphology and we could not detect blisters, erosions, or epidermal detachment from the underlying dermis,” they noted.

The patient has remained stable since being discharged from the hospital in February 2016, and requires no ointment or medications to maintain a healthy epidermis, they said.

“This approach would be optimal for newly diagnosed patients early in their childhood,” Dr. Hirsch and associates noted. “A bank of transduced epidermal stem cells taken at birth could be used to treat skin lesions while they develop, thus preventing, rather than restoring, the devastating clinical manifestation that arise in these patients.

The study was supported in part by several government grants from organizations including the Italian Ministry of Education and the European Research. Two of the researchers are cofounders and members of the Board of Directors of Holostem Terapie Avanzate, which met all costs of good manufacturing practice production and procedures of transgenic epidermal grafts.

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