Calcipotriol Ointment Seen to Improve Wound Healing in RDEB Patient, Study Finds
A low dose of calcipotriol, which is already approved for the treatment of psoriasis, may improve healing and prevent wound infections in patients with recessive dystrophic epidermolysis bullosa (RDEB), a study showed.
Treatment with calcipotriol ointment helped close a chronic wound in one patient and eliminated harmful bacteria growing inside it. The compound was also able to enhance skin cells’ defenses against microbial growth and reduce cancer proliferation in skin cells of RDEB patients.
The potential treatment is currently being evaluated in a Phase 2 clinical trial.
The study, “Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti-neoplastic effects in epidermolysis bullosa keratinocytes.” was published in the journal Nature Scientific Reports.
RDEB is caused by mutations in the COL7A1 gene, which provides instructions to make type VII collagen, a key component for the attachment of the upper skin layer, the epidermis, to its underlying layer, the dermis.
Because patients with RDEB have a severe deficiency in type VII collagen protein, they develop chronic wounds susceptible to microbial infections, which often make the injury worse. Over 90% of these patients also end up developing an aggressive form of skin cancer called squamous cell carcinoma at the wound sites.
The inflammatory process in infected wounds is believed to contribute to the development of skin cancer, so some investigators have proposed that “topical antimicrobials and local wound care are critically important in wound management and possibly cancer prevention in RDEB,” researchers wrote.
However, standard therapy for severely infected wounds in RDEB does not exist.
In the study, researchers proposed that enhancing the activity of vitamin D3 at sites of skin injury could help heal chronic wounds and control infections in RDEB.
Vitamin D3 is crucial for proper wound healing, tissue repair, and the production of antimicrobial peptides. The natural supply of this vitamin depends mainly on the skin’s exposure to the sun’s ultraviolet B rays, which drives the production of a pro-form of vitamin D3. Then, the skin and other organs are able to convert it in its active form, called calcitriol.
The researchers reasoned that in the context of RDEB, “limited sun exposure due to wound dressings and reduced outdoor activity of patients could lead to a local vitamin D3 deficiency in the skin.” If this deficiency would be counteracted, symptoms might then improve.
To test this hypothesis, scientists evaluated whether treatment with calcipotriol — a molecule that mimics active vitamin D3 and is approved by the U.S. Food and Drug Administration in skin formulations for the treatment of psoriasis (brand names Dovonex and Sorilux) — could improve wound healing and antimicrobial defense.
When RDEB epidermal skin cells (keratinocytes) grown in the lab were treated with a low dose of calcipotriol, scratches made on the cell’s layer closed more rapidly. Also, the treatment enhanced the skin cell’s release of antimicrobial compounds, which blocked the growth of harmful yeast.
Another important observation was that adding calcipotriol to skin cancer cells (squamous cell carcinoma) reduced the proliferation of these malignant cells.
Based on these promising results, researchers tested a low-dose calcipotriol ointment in a 75-year-old RDEB patient who had a chronic wound in one of his legs. The wound was completely closed within the first two weeks of treatment, and did not re-open during the remainder of the 28-day treatment phase.
As the wound healed, the type of bacteria gradually approached that of a healthy skin patch of the patient. At the start of the intervention, the wound was largely colonized by the bacteria Staphylococcus aureus, a species which may cause serious infections. But at the end of the 28-day treatment with calcipotriol, it had been completely cleared.
The patient also reported reduced itchiness and pain on the wound area after the treatment.
“The combined wound healing, anti-microbial, and anti-neoplastic [anti-tumor] effects indicate that calcipotriol may represent a vital therapeutic option for RDEB patients which we could demonstrate in a single-patient observation study,” the researchers wrote.
“Additionally, the known safety profile of calcipotriol facilitates a rapid repurposing for off-target use in DEB,” they added.
Based on the positive data, the team initiated a small Phase 2, placebo-controlled trial (CALCIDEB2016 Eudranet 2016-001967-35) to assess the efficacy of a low-dose calcipotriol ointment in wound healing in dystrophic epidermolysis bullosa.