This 2016 study—“Novel Insight into the Role of Antimicrobial (Host Defense) Peptides/Proteins in Human Skin Diseases”—in particular details how Brilacidin, modeled after defensins, could possibly be developed as a topical agent for a variety of skin disorders, such as Eczema, Acne Vulgaris, Acne Inversa (Hidradenitis Suppurativa), given its role in the cutaneous adaptive immune response, including:
· Regulation of inflammation
· Induction of cell proliferation and differentiation
· Regulation of cytokine/chemokine production
· Facilitation of cell migration
· Promotion of wound healing
· Regulation of barriers
Brilacidin’s low level of systemic absorption when topically administered (as revealed in its use in Ulcerative Proctitis/Ulcerative Proctosigmoiditis and Oral Mucositis, currently in mid-stage clinical trials), while remaining efficacious, further reinforces its therapeutic potential in treating skin diseases.
One key aspect of Brilacidin's Mechanism of Action (MOA), inhibiting Phosphodiesterase 4 (PDE4), might also contribute to its therapeutic potential in treating skin diseases. The PDE4 inhibitor apremilast (Otezla) has been evaluated in clinical trials in Hidradenitis Suppurativa and in Atopic Dermatitis, with early published case results indicating promising signs of clinical efficacy (see apremilast in HS and apremilast in Atopic Dermatitis, poster, pdf).
The human skin microbiome is influenced by bacterial infection in a complex manner. It has been hypothesized that increased susceptibility of people with atopic dermatitis to S. aureus infections, which is significantly over-expressed in this skin condition, may arise from the impaired expression of Host Defense Proteins (HDPs). And unlike Crisaborole, which was acquired in 2016 by Pfizer for $5.2 billion, Brilacidin, is highly active against S. aureus. Brilacidin might show another distinct advantage in that the drug candidate exhibits a strong inhibitory effect on IL-1, whereas Crisaborole shows no such activity. (IL-1 is linked to the pathogenesis of numerous diseases, including rheumatic disease and eczema.)