Those with recessive dystrophic epidermolysis bullosa (RDEB) have fragile, easily blistered skin. Unfortunately, because of dysfunctional tissue repair, wounds may take longer to heal – causing increased levels of scarring and other health issues. There is a huge unmet need in terms of therapies which can promote faster and more effective wound healing. But Epidermolysis Bullosa News reports that researchers recently determined that methotrexate could be an adequate therapeutic option.
To learn more about the study, take a look at the findings published in Experimental Dermatology.
What is Methotrexate?
Methotrexate is an orally administered treatment which belongs to a class of drugs called antimetabolites. Currently, methotrexate can be used to treat severe psoriasis; uterine, breast, or lung cancer; or autoimmune conditions like rheumatoid arthritis (RA). It works by slowing immune response and slowing the growth of skin cells. Learn more about methotrexate.
In RDEB research, researchers discovered that over 2,000 transcripts were differentially produced between wounds and other skin. Because of this, researchers believed that gene expression would differ between the two skin areas. As a result, it might be possible to alter or revert abnormal gene expression to promote better wound healing.
To begin, researchers collected skin biopsies from six adults with RDEB. The biopsies were sourced from areas next to poorly healing wounds, as well as unwounded skin. Next, researchers evaluated transcripts and gene expression from these samples, as well as biopsies taken from healthy controls.
Eventually, researchers found that gene expression was interrupted within the JAK/STAT signaling pathway, as well as between cytokines and Toll-like receptors. Normally, these all play a role in immune response. Because of this, these dysfunctional or poorly regulated genes caused poorly healing wounds. After determining this underlying cause, the research team then explored potential therapeutic molecules through L1000FWD, a research application.
After narrowing down potential therapeutic molecules, the four best options were determined to be:
- Simvastatin
- Anafranil
- Fulvestrant
- Methotrexate
Therefore, in the future, it might warrant further testing to determine the actual efficacy of these compounds in improving RDEB-related wound healing.
About Dystrophic Epidermolysis Bullosa (DEB)
COL7A1 gene mutations cause dystrophic epidermolysis bullosa (DEB), which exists under the greater umbrella of epidermolysis bullosa (EB). Normally, this gene encodes for the production of type VII collagen subunits, which play a role in connective tissue strength and structure. However, when there is little to no collagen production, the skin becomes fragile and easily blistered. DEB also has multiple subtypes, including:
- Recessive dystrophic epidermolysis bullosa severe generalized
- This is the most severe subtype. Many infants are born with missing or blistered skin. Blistering may occur anywhere on the body and often causes scarring, which may in turn lead to difficulty feeding or slowed growth. Other symptoms include fused skin between the fingers and toes, missing or lost fingernails and toenails, joint contractures, and eye inflammation.
- Dominant dystrophic epidermolysis bullosa
- Alternately, this is the most mild form. Blisters may form on the feet, elbows, hands, and knees. While scarring may form, it is usually not severe. People with dominant DEB may also experiencing missing or deformed fingernails or toenails.
- Recessive dystrophic epidermolysis bullosa generalized and localized
- In this form of DEB, blistering usually occurs on the hands, knees, feet, and elbows. However, if severe, it may spread to other locations. Malformed fingernails, as well as skin scarring, are also present.
