Transgenic Stem Cell Therapy Restores Skin of Boy with Rare Genetic Condition

Rare Daily Staff

A seven-year-old boy in Germany who lost 80 percent of his skin to a potentially lethal rare genetic condition that causes it to blister, rupture, and fall away, has been restored to health through an experimental process of genetically correcting the gene defect in skin cells taken from him and growing replacement skin that doctors engrafted, according to a study in Nature.

The boy, who suffered from junctional epidermolysis bullosa, or JEB, had been admitted to the Burn Unit of the Children’s Hospital, Ruhr-University in Bochum, Germany in June 2015. His prognosis was grim after all treatments had failed. There was little they could do than manage his pain.

JEB causes the skin to become fragile because of mutations to genes that affect a laminin-332, a protein that is a component of the basement membrane of the epidermis.

Doctors won approval to try an experimental therapy that had been successfully used by a team of Italian researchers led by Michele De Luca at the University of Modena, who was one of the authors of the Nature study. In the past, De Luca had developed ways to generate stem cells from human skin, use gene therapy techniques to correct genetic defects that cause disease, and grow sheets of healthy skin in the lab.

De Luca had demonstrated in a patient with JEB in 2006 that he could grow healthy skin patches from biopsies and replace small areas of lost skin. A second patient confirmed this, but the technique had only been used to treat small patches of skin and not virtually the entire skin of a patient.

Surgeons in Germany sent a biopsy taken from a non-blistering area of the boy’s body to Modena. De Luca and colleagues were able to reconstruct the epidermis. From the skin cells, the authors established primary keratinocyte cultures, which were genetically modified using a retroviral vector to contain the non-mutated form of the gene LAMB3 gene, the gene that drove the boy’s condition. Keratinocytes are a type of epidermal cell.

The surgeons performed two major skin transplants six months after proving a skin biopsy and the boy could return to school. An editorial in nature notes that, “During the many months since, he has not had so much as a blister, and loves to show off his ‘new skin’.”

Through the process of clonal tracing, the authors found that the human epidermis is sustained by a limited number of long-lived stem cells which are able to extensively self-renew and can produce progenitors that replenish terminally differentiated keratinocytes.

The authors say that the “study paves the way for gene therapy to treat other types of epidermolysis bullosa and provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies.

November 9, 2017