Gene therapy saves boy’s skin, life: study

The boy, then seven years old, was admitted to hospital in June 2015 with the “devastating” effects of a genetic disease called Junctional epidermolysis bullosa (JEB) that has tormented him since birth.

The disease causes the skin to blister and come off at the slightest touch.

Doctors were at a loss. After trying everything they knew, they concluded the child would die.

He was admitted to the Ruhr University Children’s Hospital in Bochum, Germany “because he had developed an infection in which he rapidly lost nearly two-thirds of body surface area” of the outer skin layer called the epidermis, said Tobias Rothoeft of the hospital’s burn unit.

“He was in a septic state he was severely dystrophic (wasting away), so we had a lot of problems in the first days keeping this kid alive.”

His doctors consulted experts around the world.

They tried to promote “spontaneous healing” with strong antibiotics, which did not work, then transplanted skin from the boy’s father, which was rejected.

“After nearly two months we were absolutely sure that we could do nothing for this kid and that he would die,” Rothoeft told journalists ahead of the study’s publication in the journal Nature.

– Try ‘anything’ –

As the discussion turned to making the boy’s last days as comfortable as possible, his parents urged doctors to try “anything”.

So they “studied the literature” and came across the work of Michele de Luca (SUBS: male), a regenerative medicine expert in Modena, Italy.

“He promised us he could give us enough skin to heal to heal this kid,” said Rothoeft.

De Luca and a team took skin cells from an unaffected part of the boy’s body, fixed the mutated gene, and used the corrected cells to grow skin in culture.

After permissions were obtained for the compassionate use of an experimental therapy, the skin was grafted onto the boy’s body in two operations in October and November 2015. Remaining spots were covered in a later, smaller procedure.

About 80 percent of his skin was replaced overall.

The boy was discharged from hospital in February 2016 after nearly eight months in intensive care.

Almost two years on, he is doing well and playing soccer, having gone from being on constant morphine to no drugs at all.

“The skin is of good quality, it doesn’t need any ointments or stuff like that, it’s perfectly smooth and it’s quite stable,” said Rothoeft.

– Like normal skin –

“If he gets any bruises like small kids… have, they just heal as normal skin heals… like bruises in any other kids do.”

The form of JEB the boy suffers from is caused by a mutation in a gene called LAMB3, which prevents the epidermis from anchoring properly to the underlying layer, the dermis.

There is no cure for JEB and more than 40 percent of sufferers die before adolescence. Those who survive deal with chronic wounds, and often get skin cancer.

The epidermis, tough and water-resistant, protects the body from dehydration, injury and infection.

To the team’s delight, their lab-grown skin, as in healthy people, contained stem cells crucial for long-term skin regeneration.

“I’d say that this epidermis will stay basically forever,” De Luca said.

The boy still has some blisters in non-transplanted areas — affecting about two or three percent of his body surface area.

The technique “marks a major step forward” in the field of gene and stem cell therapy, experts Mariaceleste Aragona and Cedric Blanpain wrote in a comment on the study.

It is not known, however, if it would work equally well for different forms of JEB, or in adults.

“Longer-term follow-up of the child in the current study and other patients will be needed to ensure that there are no adverse consequences — for example, the development of skin cancers,” the duo wrote.

Clinical trials are underway.