Affiliation:
1. Reviva Pharmaceuticals, Inc. Cupertino California USA
Abstract
AbstractBackgroundDopamine (D) and serotonin (5‐HT) pathways contribute to psoriasis pathobiology. Disruptions incite increased inflammatory mediators, keratinocyte activation and deterioration, and worsening symptoms. Brilaroxazine (RP5063), which displays potent high binding affinity to D2/3/4 and 5‐HT1A/2A/2B/7 receptors and a moderate affinity to serotonin transporter (SERT), may affect the underlying psoriasis pathology.MethodsAn imiquimod‐induced psoriatic mouse model (BALB/c) evaluated brilaroxazine's activity in a topical liposomal‐aqueous gel (Lipogel) formulation. Two of the three groups (n = 6 per) underwent induction with 5% imiquimod, and one group received topical brilaroxazine Lipogel (Days 1–11). Assessments included (1) Psoriasis Area and Severity Index (PASI) scores (Days 1–12), skin histology for Baker score based on H&E stained tissue (Day 12), and serum blood collection for serum cytokine analysis (Day 12). One‐way ANOVA followed by post hoc Dunnett's t‐test evaluated significance (p < 0.05).ResultsImiquimod‐induced animal Baker scores were higher versus Sham non‐induced control's results (p < 0.001). Brilaroxazine Lipogel had significantly (p = 0.003) lower Baker scores versus the induced Psoriasis group. Brilaroxazine PASI scores were lower (p = 0.03) versus the induced Psoriasis group (Days 3‐12), with the greatest effect in the last 3 days. The induced Psoriasis group showed higher Ki‐67 and TGF‐β levels versus non‐induced Sham controls (p = 0.001). The brilaroxazine Lipogel group displayed lower levels of these cytokines versus the induced Psoriasis group, Ki‐67 (p = 0.001) and TGF‐β (p = 0.008), and no difference in TNF‐α levels versus Sham non‐induced controls.ConclusionBrilaroxazine Lipogel displayed significant activity in imiquimod‐induced psoriatic animals, offering a novel therapeutic strategy.