Antonio Vento is 13 years old. He is a midget in bandages who cannot walk and, until recently, could no longer see as a shadow. He has dystrophic epidermolysis bullosa (DEB), an inherited condition that makes his skin so fragile that children with the condition are called “butterfly children.”
But thanks to a new type of gene therapy that was applied to his skin and dripped into his eyes, Antonio is now doing better. His wounds have partially healed and a recent visit to the ophthalmologist confirmed that his vision has improved significantly. “Now I can see little things,” he says in Spanish during a phone call. For example, the blocks in the video game Minecraft, which he now plays.
“And calls me Anthony,” he says. He likes that better.
Last Friday, the US Food and Drug Administration (FDA) approved Anthony’s gene replacement therapy. It’s the first commercial gene therapy to be applied topically — and also the first to be used repeatedly on the same person.
The problem with “butterfly children” like Anthony is that their bodies don’t make the kind of collagen that holds the layers of skin together. The result is chronic, blistering wounds, not only on the body, but also in the throat and sometimes in the eyes.
Gene therapy with ointment
During the treatment, a missing gene is introduced into the skin cells so that they can form collagen. The novel delivery method is already being studied for the treatment of other rare skin diseases. An inhaled gene therapy for the treatment of cystic fibrosis is also being researched.
The treatment, called Vyjuvek, was developed by Pittsburgh-based start-up Krystal Biotech and is approved for treating people older than six months with this specific form of epidermolysis bullosa. Until now, there have only been a few treatment options for the disease. According to the company, about 3,000 people in the United States are affected.
“Since he was born, I’ve been pretty much just changing bandages and healing wounds,” says Yunielkys Carvajal, Anthony’s mother, who immigrated to the United States from Cuba on a humanitarian visa in 2012 to have her son treated.
Since 2017, the FDA has approved five gene therapies for rare inherited diseases, and Vyjuvek is the sixth. However, the five earlier treatments are all given by injection or by altering immune cells outside the body. By delivering gene therapy in an ointment that is rubbed in, Krystal Biotech has achieved what CEO Krish Krishnan describes as “a simple, convenient and patient-friendly way to give these patients the missing gene.”
The company doesn’t say how much the treatment will cost. Other gene therapies have commanded record prices, with the highest price for the so-called “hemophilia” hemophilia B being $3.5 million.
relief but no cure
The gene replacement for the skin could be lucrative not only for medicine but also for cosmetics. A subsidiary founded by Krystal Biotech called Jeune has already begun testing a version of the drug on volunteers to help eliminate crow’s feet and other wrinkles that develop when the body produces less collagen as we age. It bills itself as a “gene-based aesthetics company”.
Proof that the treatment works came in a 2022 study conducted by Krystal, in which Anthony was among a total of 31 epidermolysis bullosa patients, aged between one and 44 years, who had the gene therapy ointment on the most severe ones applied to wounds. Other wounds received a placebo.
Anthony’s mother says they chose a particularly large and painful wound on his heel as part of the study. “We applied the ointment, the wound disappeared and never opened again,” she says. “It was incredible. It was a big, chronic wound and then suddenly it was gone.”
Other wounds on Anthony’s body are also shrinking, but he’s not healed as a result. His skin cells are constantly being replaced with new cells that suffer from the same genetic defect. Therefore, the therapy must be reapplied once a week by a specialist. Krystal Biotech officials say Anthony’s treatment is the first gene therapy approved for such repeated use.
Scientists today have numerous options for manipulating genes in a targeted manner. In the laboratory, cells can be fixed in a dish or even mice can be cured of deadly diseases. The treatment of humans is much more difficult, because in the process of gene transfer, corrected DNA has to be brought into a human body and anchored there.