Background: CD93, a type 1 transmembrane glycoprotein with pro-inflammatory properties, is highly expressed in macrophages and endothelial cells during advanced inflammation. The pathogenesis of Duchenne muscular dystrophy (DMD) is characterized by chronic inflammation and subsequent fibrosis of skeletal muscles due to repeated cycles of degeneration and regeneration in the absence of dystrophin. Our previous studies having demonstrated the anti-inflammatory and anti-fibrotic effects along with effects on reducing muscle fatigue, in clinical and pre-clinical studies, of Neu-REFIX, a biological response modifier exopolysaccharide beta 1,3-1,6 glucan secreted by Aureobasidium pullulans, we investigated its effects on CD93+ macrophages infiltration into the diaphragm of mdx mice.
Methods: The study included three groups of mice, studied for 45 days: (i) Wild Type (WT), (ii) mdx-Control, and (iii) mdx mice orally administered with Neu-REFIX. Diaphragm specimens (n = 14 per group) were analyzed using immunohistochemistry to evaluate CD93+ macrophages.
Results: CD93 expression in the WT group was minimal (0.07 ± 0.06). In the mdx-Control group, CD93 levels increased significantly by 31% (2.20 ± 5.86). However, Neu-REFIX administration resulted in a marked reduction in CD93 expression (0.2 ± 0.42; p < 0.0001) in the mdx-Neu REFIX group.
Conclusion: Effective management of inflammation is crucial for optimizing the therapeutic benefits of dystrophin restoration therapies in DMD. This study having proven the standalone efficacy of Neu-REFIX administration in significantly reducing inflammatory macrophage infiltration in diaphragm of mdx mice, highlight its efficacy as a disease-modifying adjuvant in mitigating inflammation, holding potential to enhance the outcome of DMD treatments, including gene therapies, which themselves can induce inflammatory responses.