The disease known as “butterfly skin” is a rare skin condition caused mainly by a genetic mutation. Researchers at Stanford University have just revealed the results of an innovative gene therapy that is in clinical trials and has been effective in the nine patients treated . The results have just been published in the prestigious journal Nature Medicine .
What is butterfly skin?
There are many diseases associated with the skin or that present their symptoms in this organ, but in many cases they are caused by complex mechanisms and multiple factors.
In this disease, epidermolysis bullosa (EB), we find several factors that together give rise to hypersensitive and fragile skin at the slightest contact . There is a type of EB where we can identify a main responsible for the appearance of symptoms: collagen. Specifically, the COL7A1 gene, which codes for the collagen VII molecule, and where a mutation causes collagen to not be produced properly. The collagen in the skin acts like a glue that holds it together and stable , and all the cells that make it up.
If collagen, or any other molecule that has a complementary function in the skin, is defective or absent, the integrity of the epidermis and dermis is completely lost. Not only can contact injuries occur, but there is no functional epithelial barrier to stop the entry of external pathogens. In addition, the symptoms are not limited to the skin, since they can also present lesions in the mucous membranes, such as the mouth and the digestive tract .
The most successful therapies in the past for this disease used stem cells for autotransplantation (link to Sarah), but it was an invasive, complicated intervention, full of side effects and that required a lot of time to develop. This new study presents an alternative and improved therapy: using a virus as a vector to introduce the correct gene .
A virus as a messenger
The researchers have designed a treatment using the herpes virus as a messenger package, where they introduce the desired gene therapy. This virus is completely harmless as it is empty of its own genes , making it unable to infect the cells of our body. This virus is applied to the skin in the form of a gel, to ensure that it is administered to the right area and stays long enough for the virus to penetrate the skin cells.
Once inside, the gene therapy kicks in by introducing perfect copies of the COL7A1 gene. With these new copies, the cells can manufacture collagen , since the defect is not in the production machinery, and thus repair wounds with proper healing.
In this phase 1 and 2 clinical trial they have included children and adults, and eight of the nine patients presented improvement in the lesions in less than three months. The researchers found that wounds that were treated with the gel healed faster and better than untreated injuries . This confirms that the treatment is effective and that its effect is local.
One of the most interesting aspects of the study is that this application has an effect in the short and medium term, since the formation of new collagen increases the stability of the skin and closes the wounds, but also keeps them closed . Collagen production was observed as early as nine days after the start of treatment, and lasted up to 100 days in one patient.
This new gene therapy does not modify the DNA of the patients’ cells , so it does not change the course of the disease dramatically, since the defective gene is not eliminated and the virus is not able to remain in the cells. Another limitation is its localized effect, which would make it necessary to apply the gel to each lesion and affected area . The researchers point out that this would be one of the next steps to reach mucosal lesions.
Both limitations are important aspects to take into account for future studies, but the benefits are unquestionably superior . The temporary and localized effect can be solved with repeated administration on the wounds, in addition to being complemented with another format for the mucous membranes. Undoubtedly, this type of therapy represents a great success for gene therapy and provides new ideas for the treatment of other skin diseases.
Phase three clinical trials are already underway with the help of the biotech company Krystal Biotech, which is responsible for the production of the gel , which can be kept at room temperature. If the results are positive, we will be one step closer to having a cure for a serious type of butterfly skin within reach, and that is good news for science and society.
Gurevich et al. 2022. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. NatureMedicine . doi: 10.1038/s41591-022-01737-yConger K. March 2022. Stanford Medicine. News Center.