An incredibly rare but debilitating skin condition has been corrected using a gene therapy applied through the skin by a gel for the first time. The work, which was published in Nature Medicine, is a milestone in a growing field of research using gene therapies in alternative ways to the traditional injection, providing hope to sufferers of the painful disorder. Recessive dystrophic epidermolysis bullosa, which causes children to have extremely fragile skin that blisters and wounds easily as well as an increased cancer risk, affects around 1 in 800,000 newborns in the US, and treatment options are extremely limited. It is one of four disorders that are part of the epidermolysis bullosa group and is a recessive genetic disorder inherited from the child’s parents. In affected children, there are mutations in the gene COL7A1, which codes for collagen VII. Collagen VII is a vital structural protein that anchors other collagen proteins to give it strength and support, and mutations in COL7A1 result in a lack of this protein. All recessive dystrophic epidermolysis bullosa disorders are a result of COL7A1 mutations. In the pursuit of a treatment option, Peter Marinkovich and a team of scientists from Stanford turned to gene therapy to add a working copy of COL7A1 back into skin cells of people with this condition. Their vector of choice, which carries the gene and inserts it into the DNA, was herpes simplex virus type-1 (HSV1), a vector with a long history in gene editing. The virus is first de-activated to stop it replicating inside the host, instead becoming a harmless delivery vehicle. After success in mice and in cultured cells, the team moved to clinical trials – the first-ever trial of topical gene therapy. A Phase 3 trial, enrolling 31 children and adults with recessive dystrophic epidermolysis bullosa, delivered the therapy in gel form as a means of directly delivering the gene-carrying vectors to the skin, where it is needed. One of the hardest challenges in gene therapy is effectively delivering the treatment to the desired place, so what better way to apply something to the skin than a gel or ointment? The trial was placebo-controlled, so each patient received one dose of gene therapy to a wound and a placebo to another; the treatment was applied once a week until the wounds closed. After 12 weeks, 71 percent of the wounds that received the therapy had healed, a significant improvement over the placebo in which only 20 percent had healed over the same period. The researchers carefully monitored any side effects and markers for the immune system reacting to the therapy, but no serious safety or efficacy concerns were reported. According to one patient from the trial, the therapy has changed his life. “The gene therapy was very good for my back. Now, I can have a bath without it burning my skin,” said Vincenzo Mascoli to New Scientist. “I hope I will be able to use it on the rest of my body.” The team now hope to apply to the Food and Drug Administration to get approval for the gel treatment in the next few months. Source
