People with recessive dystrophic epidermolysis bullosa, a genetic condition that causes widespread skin blistering, have been successfully treated by inserting new collagen genes into their skin
28 March 2022
A rare genetic skin condition has been corrected for the first time using a gene therapy that is applied to the skin.
About 1 in 800,000 children in the US are born with a severe condition called recessive dystrophic epidermolysis bullosa that makes their skin extremely fragile and prone to tearing and blistering.
“It is very painful,” says Vincenzo Mascoli, 22, who travelled from Italy to the US to have the gene therapy. He had open wounds all over his body, including one covering his entire back that had been there since he was 2 years old. “Sometimes I also get blisters in my eyes and have to keep my eyes closed, and sometimes I get blisters in my throat that make it difficult to eat – I can only have liquid food then,” he says.
Mascoli and other people with the condition have fragile skin because they have a faulty version of a collagen gene called COL7A1. That means their skin can’t produce the collagen proteins needed to give it structure and strength.
Peter Marinkovich at Stanford University in California and his colleagues developed a way to insert normal COL7A1 genes into the skin of such individuals so they can start producing collagen properly.
They did this by engineering herpes simplex virus to deliver COL7A1 genes into skin cells. This virus is normally known as the cause of cold sores, but it was modified so it couldn’t replicate or cause disease. “All it does is go into the cell and deliver the gene,” says Marinkovich.
The gene therapy was then incorporated into a gel so it could be applied to the skin. It was tested in a late-stage clinical trial in the US involving 31 children and adults with recessive dystrophic epidermolysis bullosa, including Mascoli.
For each participant, the gene therapy gel was applied to one of their wounds and an inactive gel applied to another to compare the difference. The treatment was repeated weekly until the wounds closed.
After three months, 71 per cent of the wounds treated with the gene therapy had completely healed, compared with 20 per cent of those treated with the inactive gel, and there were no serious side effects.
Mascoli’s large back wound was treated with the gene therapy and it is now 95 per cent closed. “The gene therapy was very good for my back. Now, I can have a bath without it burning my skin,” he says. “I hope I will be able to use it on the rest of my body.”
Marinkovich has been trying to develop a treatment for epidermolysis bullosa for more than 25 years. He says it is “so nice to finally have something to offer this patient population. Up until now, they’ve had nothing, there have been no specific therapies.”
A US company called Krystal Biotech has partnered with Marinkovich and his colleagues to develop the gene therapy and will apply in the next few months for approval from the US Food and Drug Administration to make it available to patients.
A major advantage of the treatment is that it can be shipped anywhere and used off the shelf, says Marinkovich.
The effects aren’t permanent because skin cells that take up the new COL7A1 genes naturally die off and get replaced, so the gel must be reapplied approximately every six months, he says.
He believes that other genetic skin disorders could also be corrected using gene therapies that can be applied to the skin. For example, Krystal Biotech is developing similar treatments for Netherton syndrome, which is caused by defective SPINK5 genes and makes the skin scaly and red, and a type of congenital ichthyosis that is caused by faulty TGM1 genes and also causes skin scaling.
Gene therapies are also being developed for non-skin conditions like amyotrophic lateral sclerosis and age-related macular degeneration, but these are more complicated because new genes must be injected into cells near the spinal cord or the back of the eye, respectively, rather than simply being applied to the skin.
Journal reference: Nature Medicine, DOI: 10.1038/s41591-022-01737-y
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