The science behind the incredible story of the ‘butterfly’ boy who had 80% of his skin replaced
In a landmark case, scientists have effectively “cured” a seven-year-old boy of a rare and devastating genetic skin disease using stem cell and gene therapy.
The disease in question, junctional epidermolysis bullosa (JEB) is caused by mutations in one of three genes – LAMA3, LAMB3 and LAMC2 – and results in skin that is extremely fragile and susceptible to blistering, infection and cancer.
The boy had lost 80% of his skin as a result of his condition and the prognosis was extremely poor after his body rejected a skin graft from his father. After the scientists exhausted all other treatment options, one of the doctors treating him at the Ruhr University Bochum in Germany got in touch with Italian stem-cell researcher Michele De Luca at the University of Modena and Reggio Emilia for advice. De Luca had previously succeeded in growing small amounts of gene-repaired skin for children with the same condition, but to successfully treat the boy, he needed to generate more than 14 times the amount of skin.
How did they do it?
The scientists took a small 4cm square patch of what little remaining skin there was on the boy and grew skin stem cells from it in a lab. Next, they used a retrovirus to insert a healthy version of the deficient LAM3 gene. They were able to grow these correct cells into sheets of skin that were grafted onto the boy during two separate surgeries.
Professor Cédric Blanpain, a stem cell scientist at the Free University of Brussels, told the Guardian the case was “a beautiful example of something that was unthinkable before the study. To replace and gene-correct the whole skin of a patient is just amazing.”
How is the boy doing now?
Incredibly, only 21 months after the treatment, the boy’s skin grafts are healthy and he is able to live a normal life. He plays football and goes to school and if his skin is damaged, he heals like any other person. A few small areas of his skin that were not treated do still blister, but it is thought the corrected stem cells might eventually replace all of his skin.
What is JEB?
The US National Library of medicine describes Junctional epidermolysis bullosa (JEB) as “one of the major forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily.” There are two types of the disease: Herlitz JEB and non-Herlitz JEB. The former is more serious and affects individuals from birth or early infancy. Blisters form as soon as the skin is subjected to even minor friction and because blisters form on the mucous membranes such as the linings of the mouth and digestive tract, eating and digesting food can be difficult. The life expectancy of individuals suffering Herlitz JEB is often less than a year because of the severity of its symptoms, while those with non-Herlitz JEB normally have a normal life expectancy. Both conditions are extremely rare, affecting fewer than 1 per million in the US.
What is stem-cell therapy?
Stem-cell therapy is where stem cells are used treat or prevent a disease. They are undifferentiated cell types that can change into specialised cell types and occur naturally in the body, replacing cells that are lost or damaged. However, they can also be generated by scientists in a lab by reprogramming “normal” adult cells. Perhaps the most common type of stem cell therapy is where blood stem cells are used to provide a healthy source of blood for people with blood conditions or those who have had cancer treatment. Patients with severe burns can have skin generated for them using skin stem cells.
What is the scope for this treatment to be used in the future?
One risk of such stem cell treatment is that genetic changes could increase the chances of skin cancer, but the study observed no such changes in the young boy. If the treatment is determined to be safe in the long run, it could be significant in treating other types of epidermolysis bullosa. The problem is, each type of genetic disorder is caused by different faults that lead to different problems with the skin. Prof Michele De Luca, from the University of Modena and Reggio Emilia, told the BBC: “The gene is different, the protein is different and the outcome may be different [for each type] so we need formal clinical trials.”