Rare Disease Report

Medical Breakthrough: Gene Therapy Skin Grafts Restore 80% of EB Patient's Skin

NOVEMBER 10, 2017
James Radke, PhD
Imagine you’re a 7-year-old child with a condition that can cause you to lose up to 80% of your body’s skin. Imagine now, that within 1 year, gene therapy has allowed your body to be covered in new, blister-free skin, deeming you free to go outside and play with your friends.

Such a miraculous story happened recently when a 7-year-old-boy with junctional epidermolysis bullosa (EB)—a rare, and very severe form of EB in which patients skin is unable to properly heal properly – was introduced to the burn unit team at the Children’s Hospital of Ruhr University in Bochum, Germany.

Even the slightest bump can lead to poor healing and infections for EB patients, and most spend a good portion of their days wrapped in bandages and covered in ointment to protect the skin from further damage as the skin tries to heal.

This condition took a turn for the worse in the aforementioned 7-year-old boy due to an infection with Staphylococcus aureus and Pseudomonas aeruginosa that left him without skin on 60% of his body and all treatment options failing to stop the progression. 

As the boy’s health continued to decline, the team worked quickly to develop genetically-modified skin grafts to help him grow his own skin (at the time of the grafts, he had lost 80% of his skin). The results are this week’s cover story in Nature.

A 4 cm2 patch of skin from a non-blistering area was used to create keratinocute cultures that were transduced with a retroviral vector expressing the boy’s missing gene (LAMB3). Those cells were used to grow genic epidermal grafts to the point that all of the boy’s limbs, flanks and the back were treated with grafts over a 2-month period (October and November 2015). Remaining areas received grafts in January 2016 and in the end, about 80% of his surface area was restored by the transgenic epidermis.

One of the unique features of the skin grafts was that its methodology could not just prove to be helpful to EB patients, but could also potentially revolutionize how skin grafts are used in general. The key is diversity, as the grafts contained a mixture of holoclones, meroclones and paraclones

While holoclones are the cells that contain the new genetic material that will grow and regenerate, the graft also contained meroclones and paraclones, which are transient amplifying progenitors. These 2 cells do not rejuvenate and eventually die, but they provide stability early on. In this case, they were eventually replaced by the growing holoclones.

In their concluding remarks, the authors wrote, “transgenic epidermal stem cells can regenerate a fully functional epidermis virtually indistinguishable from a normal epidermis, in the absence of related adverse events so far. …. The successful outcome of this 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.”

Kirsch T, Rothoeft T, Teig et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature. Published online ahead of print, November 8, 2017. doi:10.1038/nature24487

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