Novel Oral Treatment for Atopic Dermatitis: Allosteric Modulation of GABAA Receptor Signaling

Abstract Background: This study explores the development of a groundbreaking oral treatment for atopic dermatitis (AD) by investigating the effects of allosteric modulators targeting the gamma-aminobutyric acid type A (GABAA) receptor outside the brain. Methods: To induce the AD phenotype, mice strains including Swiss Webster, Balb/c, and C57/BL6 received Calcipotriol (MC903) applied to both ears. The experimental groups were treated with either the novel GABAA receptor ligands, vehicle, or positive control compounds. Over a seventeen-day period, various parameters such as animal weight, ear thickness, and scratching behavior were monitored. Post-study, mice were euthanized, and gene expression and histology of their ears were examined. Statistical analysis employed a 2-way ANOVA. Results: Our findings indicate a significant reduction in the induction of inflammatory genes especially for the thymic stromal lymphopoietin (TSLP) in response to the MC903-induced AD phenotype when treated with GABAA receptor ligands. A notable reduction in scratching behavior was observed, especially when treated after the establishment of the AD phenotype. Conclusion: The administration of GABAA receptor ligands demonstrated a substantial reduction in ear inflammation, ear thickness, and ear scratching in the murine model for AD. This research provides promising insights into the development of a novel and effective oral treatment for AD.