Extension Phase of a Multi-Center, Randomized, Blinded Clinical Study Evaluating the Efficacy and Safety of a Novel Topical Product for Facial Dyschromia.

BACKGROUND: Dyschromia can be associated with increased production and/or reduced clearance of pigmentation in the skin. Multiple pathways are involved in causality. A novel topical product was recently developed, which contains actives that have been validated through in-vitro and clinical studies to counteract pigmentation related to photodamage, PIH, and melasma. This study further evaluates the safety and efficacy of this product for facial dyschromia during an additional 3-month extension period following the completion of the previous 12-week multi-center trial.  Study Design: Subjects from the previous multi-center trial with mild to severe facial dyschromia at baseline were eligible to participate in this 3-month extension study upon completion of that trial. This extension study evaluated the continued use of the novel topical product with PATH-3 Technology (Alastin Skincare, Carlsbad, CA) over a 3-month period. Subjects who were previously randomized to the novel topical product continued using it and for those previously randomized to hydroquinone 4% discontinued its use. Both cohorts continued daily sunscreen use. Blinded investigators assessed subjects at follow-up visits at 16, 20, and 24 weeks. RESULTS: Twenty-six (26) subjects completed the extension phase of the pivotal trial, with 13 subjects in each of the AL and HQ-BREAK cohorts. Significant improvements were seen within the AL cohort from weeks 12 to 24 for facial dyschromia (P=0.0158) and skin tone/clarity/evenness (P=0.0067), while there were no significant improvements seen in the HQ-BREAK cohort. The HQ-BREAK cohort had more subjects who worsened with facial dyschromia and skin tone/clarity/evenness. For the mMASI, the HQ-BREAK cohort demonstrated regression at week 24 compared to week 12, while the AL cohort instead experienced continued improvement. This difference was found to be significant (P=0.02). No study-related adverse events were reported for either cohort.  Conclusion: A novel topical product designed to counteract various steps in pigmentation pathways using PATH-3 Technology has been demonstrated to be safe and effective in treating facial dyschromia on a long-term basis. In contrast to the significant rebound experienced by subjects with HQ, the AL cohort continued to demonstrate ongoing improvement. J Drugs Dermatol. 2024;23(1):1266-1270.     doi:10.36849/JDD.7622.

Multicenter evaluation of a topical antioxidant serum.

BACKGROUND: A new antioxidant serum has been formulated with sodium ascorbate, a sodium salt of Vit C, which aims to address facial photodamage while maintaining a low irritation profile and preserving elastin. Detailed background science has been submitted in a previous publication. This open-label study was conducted to validate the science by demonstrating product efficacy and tolerability in patients with moderate to severe facial photodamage. METHODS: A multicenter, open-label clinical study was undertaken over 5 months from March 2023 to July 2023. Thirty six eligible participants (35 female, 1 male), aged 38-69 years, and Fitzpatrick skin types II-V were enrolled into and completed the study following 12 weeks of the topical antioxidant serum use twice daily, along with the following supporting products (gentle cleanser, moisturizer, and sunscreen for as needed use). Follow-up visits were conducted in Weeks 2, 4, 8, and 12. At every visit, participants were evaluated for facial photodamage severity and test product tolerability. Additionally, study participants underwent subject assessments and satisfaction questionnaires, investigator assessments, biopsy collection, and photography. RESULTS: Significant improvements in all evaluated facial photodamage parameters were observed at 12 weeks together with excellent tolerability and subject satisfaction persisting to Week 12 at study completion. Histology most notably revealed increased elastin fibers in 5 out of 5 post 12-week treatment biopsies on Movat staining, while Herovici stains revealed stimulation of collagen and early formation of new fibers. CONCLUSION: A novel antioxidant serum has demonstrated to be safe and effective for addressing facial photodamage, while stimulating the production of both elastin and collagen in the extracellular matrix (ECM).

WATCH VIDEO ABSTRACT: Dermatoporosis: Strategies for Rebuilding the Extracellular Matrix of the Skin.

Dermatoporosis as a disease entity is relatively newly described, the title conceived as recently as 2007. The background of chronic skin fragility, bruising, and atrophy appears to start in some patients as early as their mid-forties, but is full blown over the age of 65 years. The dehydration and fragility of the skin with recurrent bruising and breakdown were initially attributed to increased vessel fragility and permeability thought to be associated with inherent vascular tissue defects in a milieu of increased inflammation and extracellular matrix (ECM) degradation. It has subsequently been demonstrated that this ECM breakdown directly affects the structural support system of the superficial vessels, leading to stretch, increased permeability, and vulnerability to mechanical damage. Add to that the ECM atrophy and general accumulation of non-functional metabolic waste products in the form of fragmented collagen, elastin, and increased circulating glycation end products, and it becomes apparent that much of the problem resides in a structural defect, non-functioning, dehydrated, senescent cellular matrix and unsupported vascular system that presents as dermatoporotic characteristics. This paper describes a strategy of ECM replacement to counteract these foundational deficiencies. J Drugs Dermatol. 2023;22(9): doi:10.36849/JDD.7549.

Identification of an intracellular M17 family leucine aminopeptidase that is required for virulence in Staphylococcus aureus.

Staphylococcus aureus is a highly virulent bacterial pathogen capable of causing a variety of ailments throughout the human body. It is a major public health concern due to the continued emergence of highly pathogenic methicillin resistant strains (MRSA) both within hospitals and in the community. Virulence in S. aureus is mediated by an array of secreted and cell wall associated virulence factors, including toxins, hemolysins and proteases. In this work we identify a leucine aminopeptidase (LAP, pepZ) that strongly impacts the pathogenic abilities of S. aureus. Disruption of the pepZ gene in either Newman or USA300 resulted in a dramatic attenuation of virulence in both localized and systemic models of infection. LAP is required for survival inside human macrophages and gene expression analysis shows that pepZ expression is highest in the intracellular environment. We examine the cellular location of LAP and demonstrate that it is localized to the bacterial cytosol. These results identify for the first time an intracellular leucine aminopeptidase that influences disease causation in a Gram-positive bacterium.