Hassan is only 9 years old, but he has suffered much more than a lifetime. Every single day, especially the first seven years, his life was overshadowed by a deadly disease. However, after a breakthrough operation, now he can go to school, play football and live a normal life like any other boy.
Hassan was diagnosed with epidermolysis bullosa (EB) shortly after birth. His family were told that there was no cure for the disease. One year after Hassan and his family moved to Germany, escaping the war in Syria, Hassan’s condition got worse. EB is a rare inherited skin disorder. Sufferers have genetic mutations on one of the genes that helps produce the protein which attaches the upper layers of skin to deeper layers. As a result of the mutation, sufferers’ skin can become blistered from just a mild bump or friction. Patients with EB are sometimes called ‘butterfly children’ because their skin is as delicate as a butterfly’s wings. Complications from the disease can include skin cancer and deadly infections.
Hassan’s disease is considered the most severe form of the condition – sufferers can have trouble eating as blistering can also occur within the body. Around 40 percent of children with the condition won’t survive their first year, and most don’t live past five. In June 2015 when Hassan was 7 years old, he was admitted to the burns unit of a children’s hospital in Bochum,
Germany. By that time, around 60 percent of his epidermis – the top layer of his skin – was gone. His back, flanks, and limbs had become a continuous landscape of untreatable open wounds, red and raw. Much of it was badly infected. The pain was excruciating. Dr Tobias Rothoeft, a paediatrician at the Children’s Hospital who treated Hassan, described the deadly condition of his body at admission: “He suffered from severe sepsis (a blood infection) with high fever, and his bodyweight had dropped to a mere 17 kilograms (37 pounds) – a life-threatening condition.”
Five weeks later, Hassan’s doctors had run out of options and were planning to start end-of-life care; trying to make him as comfortable as possible after all other attempts to heal him had failed.
It was the time when Hassan’s father asked for experimental treatments, so doctors in Germany reached out to Michele De Luca, an expert in stem cell biology at the University of Modena and Reggio Emilia in Italy. They wanted to see if it would be possible to transplant genetically modified stem cells onto Hassan’s body that would correct the mutation that causes EB and generate new, healthy skin. “Dr De Luka has promised to give us enough skin to heal this kid,” Dr Rothoeft told Hassan’s father.
Stem cells have the ability to turn into any type of tissue. De Luca’s team had previously shown that such a technique could be feasible for EB patients by transplanting a few sheets of skin grown from stem cells in the lab onto a patient’s legs. Doctors took a small square of healthy skin from a non-blistering part of Hassan’s body, and De Luca’s lab in Italy used that skin to create the genetically corrected stem cells which could grow into sheets of skin for grafting. The sheets looked like clear plastic.The surgeons spent two months grafting the skin grown in their labs onto the boy’s body through three surgeries replacing about 80 percent of the skin. He spent months recovering, covered in bandages, before being discharged from the hospital in February 2016.
The new epidermis was attached like a patchwork quilt, covering almost his entire body. Within a month, the graft had integrated into the lower layers of skin. “Once the epidermis has regenerated, the stem cells keep making the renewal of the epidermis as in a normal (healthy person),” said De Luca. “All the data we have … are telling us that this is going to be a stable situation.”
Two years on, the skin is healthy, he doesn’t need to take medication or use ointments and when he gets a cut it heals normally. A potential risk of the treatment is that the introduction of genetic changes could increase the chances of skin cancer – although the study found no evidence that dangerous mutations had been caused.
In 1983, two boys accidentally set themselves on fire. More than 97 percent of their bodies were burned. Their lives were saved by the physician Howard Green, who grafted regenerated skin onto the burned parts. Green’s technique has since saved countless lives and fuelled the entire fields of stem-cell biology and regenerative medicine.
De Luca studied with Green in the early part his early career, and this procedure is almost identical to the one his mentor developed, except for one crucial part. He added gene therapy to the mix, modifying the stem cells behind the regenerating skin to correct the mutations behind Hassan’s condition. “What is nice about this study is the combination of gene and cell therapy together,” said Higgins, whose own work focuses on skin regeneration. “The success of this combined cell and gene therapy will have huge implications for the field of regenerative medicine and the treatment of genetic diseases.”
An article in The Atlantic, dated Nov 8, 2017, revealed that De Luca’s team is now running two separate clinical trials to test their gene-corrected skin grafts on around two dozen children with EB. His ultimate goal is to develop an effective and standardised procedure that could be carried out during early childhood, to prevent the painful blisters before they happen, rather than restoring lost skin after the fact. “It will take years to get there but it’s clearly doable,” he says. “Maybe this will be the last thing I’ll do in my career.”