Source: iStock / Andrey Prokhorov

A 7 year old boy with Junctional Epidermolysis Bullosa (JEB) has been successfully treated using autologous transgenic skin grafts, according to a new report. The case, reported in Nature yesterday, details the treatment of the unnamed patient with a combination of ex vivo cell and gene therapy, resulting in a significant recovery.

JEB is a genetic skin condition that affects just under 500,000 people worldwide. The disease causes patients’ skin to become very fragile, blistering even under gentle contact, and can make them more susceptible to infections and skin cancers; more than 40% of patients die before they reach adolescence. It is typically caused by mutations in three genes, LAMA3, LAMB3, and LAMC2, which encode the membrane component laminin-332. At present there is no cure for JEB and treatment usually relies on daily bandaging that is both painful for patients and very expensive long-term.

This case concerns a boy who was admitted to the Burn Unit of the Children’s Hospital, Ruhr-University in Germany in 2015 with an epidermis loss of 60%. Testing revealed that he had a mutation in the LAMB3 gene, but treatment options were very limited and the extent of skin damage was such that the patient was at very high risk of sepsis and infections. A previous single-case study had indicated that transplantation of a transgenic epidermal culture could help JEB patients, but in that instance, the transplant was only 0.06m2 in size. This boy needed a transplant closer to 0.85 m2. Nonetheless, the risk to the child was sufficiently high that the District Council of Arnsberg, North Rhine-Westphalia, Germany granted the medical team compassionate use of the treatment.

Red indicates denuded skin, green areas were blistered, and flesh-coloured regions were unblistered. Both red and green areas received transgenic skin grafts. Soure: Nature

Led by Professor Michele de Luca from the University of Moderna and Reggio Emilia, the team harvested a small patch of skin (about the size of a postage stamp) from the boy’s groin and infected the cells with retrovirus carrying a healthy LAMB3 gene. The sample was grown into sheets that were between 50 and 150 cm2, which were then grafted onto the patient, who at the time of the surgery was displaying an epidermis loss of 80%.

Two years later, no blisters have grown on the grafted areas and the patient is significantly healthier. During the 21 months of monitoring that the team kept up after the surgeries, they observed that most of the initial graft cells had disappeared in the first few months. Instead, the strengthened epidermis was maintained by a small population of long lived holoclone cells, which renewed healthy cells as they died.

They also believe that use of a retrovirus, which have previously been linked to increased chance of cancer, has not significantly impacted the boy’s risk. At present, he is cancer free and there are no implications that will change.

The team behind the paper have said that their work may be able to help many other patients with JEB around the world, but not all of them. One of the major drawbacks of this approach is that it is unable to treat any damage done to internal surfaces, such as the lining of the oesophagus, and thus may not be able to ‘cure’ patients entirely. It is also important to note that some forms of epidermolysis bullosa are not cause by a missing protein, but instead by an active, dysfunctional protein, which this treatment approach would be unable to resolve.