Clinical Trial of Alpha and Beta Defensin Skin Care Regimen for Improvement of Periocular Wrinkles

September 2023 | Volume 22 | Issue 9 | 874 | Copyright © September 2023


Published online August 17, 2023

doi:10.36849/JDD.7184

Nina Hartman MDa, Jameson Loyal MDa, Amy Taub MDb, Sabrina Fabi MDa

aCosmetic Laser Dermatology, San Diego, CA
bAdvanced Dermatology, Lincolnshire, IL

Abstract
Background: Defensins recruit leucine-rich repeat-containing G protein-coupled receptor 6 positive (Lgr6+) stem cells which ultimately regenerate new basal stem cells, healthy keratinocytes, and nascent hair follicles. Thus, defensins are an exciting, novel therapy for the reversal of skin aging.
Methods: This is a multicenter, prospective, open-label clinical trial. Twenty healthy subjects, aged 45-80, with Fitzpatrick skin types II-IV were enrolled in the study. A skin care regimen containing alpha-defensin 5 and beta-defensin 3 were applied to the face twice daily for 12 weeks. This skin care regimen contains a greater percentage of defensins than that already studied.7 All participants underwent imaging at baseline, day 30, day 60, and day 90. Primary endpoints included investigator scoring on the Fitzpatrick-Goldman wrinkle scale and percent improvement in periorbital wrinkles, laxity, pigmentation, erythema, texture, and radiance. Secondary endpoints were investigator Global Aesthetic Improvement Score (GAIS), subject GAIS, and investigator assessment of tolerability. A final subject questionnaire was completed on day 90. 
Results: Based on the Fitzpatrick-Goldman wrinkle scale, a statistically significant improvement was noted in both wrinkling and elastosis from baseline to day 90. 30% of subjects were rated as much improved and 50% of subjects were rated as improved on the physician GAIS at the 90 day follow up. Improvements were noted in all aspects of skin quality including wrinkles, laxity, dyschromia, erythema, texture, and radiance. 
Conclusion: The enhanced formula containing increased concentrations of alpha-defensin 5 and beta-defensin 3 is a safe and efficacious topical therapy for the treatment of periorbital rhytids.

Citation: Hartman N, Loyal J, Taub A, et al. Clinical trial of alpha and beta defensin skin care regimen for improvement of periocular wrinkles. J Drugs Dermatol. 2023;22(9):874-880. doi:10.36849/JDD.7184

INTRODUCTION

Skin aging is clinically characterized by xerosis, rhytids, dyschromia, atrophy, and skin laxity. It is a complex process involving both intrinsic and extrinsic elements. Intrinsic factors are numerous and still under investigation. They include, but are not limited to, telomere shortening/instability, genomic instability/mutations, stem cell exhaustion, protein, and cellular damage, increased inflammation, cell senescence, and impaired intercellular communication.1,2 Extrinsic factors contributing to skin aging are also plentiful and most notably include UV exposure, smoking, and poor nutrition. Histologically and molecularly, aged skin is characterized by epidermal atrophy, flattening of the rete ridges, decreased dermal thickness, deterioration of elastic fibers, fragmented and thickened collagen fibrils, and an increase in the collagen III to collagen I ratio.1 

Despite the myriad of tools now available for prevention and repair of aged skin such as injectable fillers, neuromodulators, laser, radiofrequency, ultrasound devices, and surgical procedures, cosmeceuticals remain a cornerstone of the market. Research over the past two decades has emerged supporting the use of stem cells, growth factors, peptides, and exosomes as key ingredients in topical anti-aging regimens.3,4 Despite promising data, variation in final product, impurities, and nonspecific targets plague these complex sources.4 

Alpha- and beta-defensins are naturally occurring antimicrobial and healing molecules that represent a novel treatment modality for skin rejuvenation. Within the skin, stem cell niches exist in the epidermis and adnexal structures and are critically important to skin homeostasis and regeneration. Notably, leucine-rich repeat-containing G protein-coupled receptor 6 positive (Lgr6+) stem cells which reside above the hair bulge, often referred to as the skin's master stem cell, create the epidermis and appendages early in utero and maintain their multipotency after birth as they are able to differentiate into both epidermal and adnexal structures.5 In addition to their roles in innate immunity, deterring microbial colonization, and reducing paracellular permeability, defensins have been found to induce wound healing via the recruitment of these Lgr6+ stem cells.5