Resolution of fibrosis in mdx dystrophic mouse after oral consumption of N-163 strain of Aureobasidium pullulans produced β-glucan

Recent advances in the management of Duchenne muscular dystrophy (DMD), such as exon skipping and gene therapy, though have reached a clinical stage, the outcome at its best is still considered suboptimal. In this study, we evaluated a novel N-163 strain of Aureobasidium pullulans produced beta-glucan (Neu-REFIX) for its potential as an adjuvant to slow down the progression of the disease by anti-inflammatory and anti-fibrotic effects. In this study, 45 mice in the three groups, 15 each in a group; Gr. 1 normal mice, Gr.2 mdx mice as vehicle, and Gr.3 mdx mice administered the N-163 beta-glucan for 45 days. The N-163 beta-glucan group showed a significant decrease in the plasma ALT, AST, and LDH levels (126 +/- 69 U/l, 634 +/- 371 U/l, 3335 +/- 1258 U/l) compared with the vehicle group (177 +/- 27 U/l, 912 +/- 126 U/l, 4186 +/- 398 U/l). Plasma TGF-beta levels increased, and plasma IL-13 levels decreased in the N-163 group. The inflammation score of HE-stained muscle sections in the N-163 group (1.5 +/- 0.8) was lower than that in the vehicle group (2.0 +/- 0.8). The N-163 strain beta-glucan group (24.22 +/- 4.80) showed a significant decrease in the fibrosis area (Masson's Trichrome-positive area) compared with the vehicle group (36.78 +/- 5.74). The percentage of centrally nucleated fibres evaluated by Masson's trichrome staining was 0 in the normal group, while it increased to 80% in the vehicle group but remained at 76.8% in the N-163 group. The N-163 beta-glucan group showed a significant decrease in the fibrosis area. Considering their safety and easy oral consumption, Neu-REFIX beta-glucan could be worth large multicentre clinical studies as adjuvant in slowing down the progress of DMD.

Automated summary

In this study, a novel strain of Aureobasidium pullulans produced β-glucan (Neu-REFIX) was evaluated as a potential adjuvant therapy to slow down the progression of Duchenne muscular dystrophy (DMD) by exerting anti-inflammatory and anti-fibrotic effects. The results showed significant decreases in plasma liver enzyme levels and fibrosis area, as well as improvements in markers of inflammation and muscle damage in the N-163 β-glucan group.