New Skin for 7-Year Old Boy Marks Advance -- WSJ

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New Skin for 7-Year-Old Boy Marks Advance in Gene Therapy
By Amy Dockser Marcus
Nov. 8, 2017 1:00 p.m. ET

Researchers transplanted genetically modified skin onto a boy with a life-threatening genetic disorder. The skin now covers approximately 80% of his epidermis
Epidermolysis Bullosa is a family of rare, often lethal, skin-blistering diseases that affect around 1 in every 20,000 births in the U.S., including this 3-year-old girl in Minnesota. Researchers were able to replace 80% of the skin on a boy with a severe form of the disease.

Epidermolysis Bullosa is a family of rare, often lethal, skin-blistering diseases that affect around 1 in every 20,000 births in the U.S., including this 3-year-old girl in Minnesota. Researchers were able to replace 80% of the skin on a boy with a severe form of the disease.

In a significant advance in organ regeneration and gene therapy, researchers created a new, healthy skin that covers almost the entire body of a 7-year-old boy with a life-threatening genetic disorder associated with skin blistering.

The new skin remains functional after 21 months, and doesn’t blister or require ointment or medication, according to the team of scientists and doctors from Austria, Germany and Italy who described the case in a paper in the journal Nature.

The child in the study has Junctional Epidermolysis Bullosa (JEB), part of a family of rare, often lethal, skin-blistering diseases. Epidermolysis Bullosa affects only around 1 in every 20,000 births in the U.S.; JEB is a severe form of the disease, often leading to death in early childhood.

Skin is the body’s largest organ. The top layer, or epidermis, protects the body from the outside environment and is anchored to the dermis below.

There are three main forms of epidermolysis bullosa, caused by mutations in genes that produce proteins essential to holding the skin’s layers together. In patients with the condition, the slightest touch or bump can cause blisters, excruciating pain and open wounds that don’t heal. There is no cure.

In the Nature study, scientists took a small piece of tissue, about the size of a postage stamp, from an unaffected part of the boy’s skin and grew cells in the lab. They then used a deactivated retrovirus to insert a correct copy of the defective gene into the patient’s skin cells and grew sheets of new skin.

In three separate operations at the end of 2015 and the beginning of 2016, they transplanted the genetically modified skin onto the boy’s limbs, flanks and back. Over time, the new skin regenerated to cover approximately 80% of the boy’s epidermis.

Other patients with the condition have been treated with genetically modified skin, but the case described today is unusual. “We had never treated that amount of skin,” says Michele De Luca of University of Modena and Reggio Emilia in Modena, Italy, and senior author on the Nature paper.

Paul Knoepfler, a professor in the department of cell biology and human anatomy at the University of California Davis School of Medicine, said doctors will need to closely monitor the patient for years, particularly because the virus used to deliver the correct gene to the cell could potentially cause other health problems.

Nonetheless, he said, the experiment is an advance for organ regeneration. “The scale is amazing,” said Dr. Knoepfler, who isn’t involved in the study.
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Gene therapy is viewed as a promising area for treating epidermolysis bullosa. Last year, scientists at Stanford University School of Medicine reported they grafted genetically corrected skin on open wounds in four adult patients with a different form of the disease. The grafts helped improve wound healing. Abeona Therapeutics Inc. is now collaborating with Stanford to open a new trial next year that will include patients ages 13 and older.

Earlier this year, Fibrocell Science Inc. announced it is testing gene therapy in a small trial involving six adult patients with a form of epidermolysis bullosa. And Krystal Biotech Inc., a gene-therapy company, said it had received funding from two nonprofits that fund research in epidermolysis bullosa to help advance its gene therapy candidate.

Gene therapy isn’t currently able to correct all gene mutations that cause epidermolysis bullosa. But if proven effective, the approach may eventually offer a way to treat symptoms as they emerge and prevent the most devastating aspects of the condition, said Peter Marinkovich, an associate professor of dermatology at Stanford and one of the senior authors on a different gene-therapy trial last year.

Tobias Hirsch, a surgeon at Ruhr University in Bochum, Germany, and an author of the Nature paper, described in a press briefing Tuesday how the boy’s condition had been so severe upon arrival at the hospital that doctors “were sure we could do nothing, and he would die.”

Five weeks after admission, with antibiotics and other efforts failing to help, the boy’s parents asked if there were any experimental treatments available. Doctors contacted Dr. De Luca, who was part of a group that previously transplanted genetically modified skin into a much smaller area in two patients.

Dr. De Luca says the genetically corrected cells in the boy’s skin continue to “behave like they are supposed to,” and the growth of the epidermis remains normal.

The child still gets blisters in areas of the body where doctors didn’t transplant new skin. The medical team has discussed whether they should do an additional transplant, the researchers said.

According to the doctors, the child in the study is back at school and plays soccer.