Trials of new gene therapy cure ‘butterfly children’ of open wounds that had not healed for years

A gene therapy applied directly to the skin has cured nine patients who were suffering from a rare disease that causes blistering, wounding and scarring as a result of even the lightest contact. Some lesions can remain open for years without closing.

Epidermolysis bullosa is a combination of genetic disorders that cause this hypersensitivity of the skin. The nine patients treated in the trial – three of whom were children or teenagers – suffered one of the most serious forms of the condition. A defect in the COL7A1 gene means that these people were unable to synthesize the collagen VII protein, which keeps together the two outermost layers of the skin: the epidermis and the dermis. The result is that even the mildest touch can cause sores and lesions over the entire body. This includes the mucous membranes that cover the mouth and the digestive tract. These patients have been nicknamed “butterfly children,” given that the disease starts to develop from birth and leaves the skin as delicate as the wings of the insect.

This trial, which was led by researchers at Stanford University in the United States, used an engineered herpes virus containing two healthy copies of the COL7A1 gene. When the deactivated pathogen enters the cells, they begin to produce the protein that corrects the disease.

The most striking part of this gene therapy is that it is applied directly onto the skin via drops, without even needing contact with the wounds. The results of the trial with the nine patients show that the majority of the sores were cured after the treatment and remained closed for at least three months. The untreated sores, however, healed much less. One of the patients was a 10-year-old girl with a chronic chest wound that had been open for four years. The first application reduced the wound by 70%, and it was completely closed after the second round of treatment.

“This therapy strengthens the skin and breaks the cycle of chronic opening and scarring of wounds in the patients,” explained Peter Marinkovich, a dermatologist at Stanford University and the main author of the study, which was published this week in Nature Medicine.

This is the first time that gene therapy has been used against this disease, and also the first use of this type of therapy directly on the skin, the authors of the research point out. Until now, the most successful experimental treatments were graft transplantations. First, a sample is taken of the patient’s skin and the cells treated to correct the genetic defect. Then the tissue is grown until nearly a square meter of healthy skin has been obtained, and it is then transplanted to the patient.

Side effects

This method was successful for some children, who recovered the capacity for wound healing and began to live a normal life. But it was a complicated procedure, and involved major side effects.

By contrast, this new treatment does not need hospitalization. On the one hand, it has a disadvantage in that it does not permanently correct the genetic defect. But on the other, it can be regularly administered without serious side effects, according to the medical team behind the trial. After the treatment, the researchers took biopsies from the participants’ wounds. The results showed that just a few days after receiving the medication their cells were already producing the collagen VII needed for the wounds to close.

The next step for research will be to apply the treatment to mucous surfaces such as the oropharynx, esophagus or eyes, explain the authors of the study. “In total, the preliminary conclusions and treatment advances described here have far-reaching implications with the potential to broadly transform the gene therapy field,” the authors state. The new treatment will be developed by biotechnology firm Krystal Biotech, which is based in the United States. The team has already begun the last phase of the clinical trials.