A Novel Peptide to Boost Epithelial Barrier Protection and Prevent Infections

Stanford researchers have developed EphrinA3 technology to strengthen epithelial barriers by increasing expression of cell-cell adhesion molecules, particularly desmoglein-1 (DSG1) and desmocollin-1 (DSC1). The vagina is lined by stratified squamous epithelium (SSE) that protects against mechanical injury and microbial infection (e.g. HIV, HSV, etc.). Circulating estrogen supports these functions, but the loss of estrogen caused using progestin-only contraceptives or onset of menopause promotes both loss of desmosome expression and the epithelial barrier, which increases susceptibility to sexually transmitted infections.

Stanford investigators discovered ephrin A3 (EFNA3) mimetic agonist peptides (EFNA3-MAP) that promote desmosome expression and strengthen the epithelial barrier. Intravaginal administration of these agents to progestin-treated or ovariectomized mice reversed the loss of vaginal epithelial barrier protection in these mice caused by lower levels of circulating estrogen. Researchers also found cutaneous EFNA3-MAP topical application reduced allergen-specific IgE in a mouse atopic dermatitis model, suggesting potential clinical utility for enhancing epithelial barrier protection.

This nonsteroidal, nonhormonal EFNA3-MAP technology has the potential to treat a range of skin conditions caused by epithelial barrier dysfunction, and improve vaginal epithelial health in women using progestin-only contraceptives (e.g., Depo-Provera), menopausal or postmenopausal women, and women with ovarian failure due to chemotherapy.

Stage of Development: Research in vivo

Researchers demonstrated treatment with EFNA3-MAP increased DSG1/DSC1 expression, and improved epithelial barrier function. In mouse models, they showed EphrinA3 treatment protected mice from HSV infection, improved vaginal epithelial integrity in a mouse model of menopause, and improved skin barrier function in a model of atopic dermatitis. Research is ongoing including toxicity studies and methods for sustained release.