Enhanced expression of Dystrophin, IGF-1, CD44 and MYH3 in plasma and skeletal muscles including Diaphragm of mdx mice after oral administration of Neu REFIX Beta 1,3-1,6 glucan

• Published in: bioRxiv
• Main Authors: Senthilkumar Preethy, Sakamoto, Shuji, Higuchi, Takuma, Ichiyama, Koji, Yamamoto, Naoki, Ikewaki, Nobunao, Iwasaki, Masaru, Vidyasagar Devaprasad Dedeepiya, Subramaniam Srinivasan, Rajmohan, Mathaiyan, Senthilkumar, Rajappa, Abraham, Samuel Jk
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.02.2025; Cold Spring Harbor Laboratory
• Edition: 1.2
• Subjects: CD44 antigen; Diaphragm; Duchenne's muscular dystrophy; Dystrophin; Enzyme-linked immunosorbent assay; Genetic disorders; Genetics; Glucans; Immunohistochemistry; Insulin-like growth factor I; Insulin-like growth factors; Oral administration; Plasma; Skeletal muscle; Japan; β-glucan; MYH3; mice; Duchenne Muscular Dystrophy (DMD); CD44
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2023.06.06.543858

Introduction: Duchenne muscular dystrophy (DMD) is a rare genetic disease, causing muscle degeneration due to lack of dystrophin with inadequate muscle regeneration culminating in muscle dysfunction. The N-163 strain of Aureobasidium Pullulans produced Beta-1,3-1,6-glucan (Neu REFIX) reported to be safe with anti-inflammatory and anti-fibrotic efficacy earlier, herein we evaluated its effects on muscle regeneration in mdx mice. Methods: Forty five mice in three groups (n=15 each): Group 1 (normal), Group 2 (mdx control), and Group 3 (mdx fed Neu REFIX) were evaluated for 45 days. IGF1, Dystrophin, CD44 and MYH3 in diaphragm, plasma and skeletal muscle were evaluated by ELISA and immunohistochemistry. Results: Mean IGF1 expression was 20.32% and 16.27% higher in plasma (p = 0.03) and diaphragm respectively in Neu REFIX group. Mean dystrophin was higher in Neu-REFIX group by 70.3% and 4.7% in diaphragm and plasma respectively than control. H score intensity of CD44+ was >2.0 with an MYH3 positivity 20% higher in Neu REFIX than control. Conclusion: Oral administration of Neu REFIX was safe. Significantly enhanced plasma IGF1 beside increased Dystrophin, MYH3 and CD44, proving a restoration of muscle regeneration and differentiation, especially in diaphragm, makes us recommend it as a disease modifying adjuvant in both early and advanced stages of DMD.Competing Interest StatementAuthor Samuel Abraham is a shareholder in GN Corporation, Japan which holds shares of Sophy Inc., Japan., the manufacturers of novel beta glucans using different strains of Aureobasidium pullulans; a board member in both the companies and also an applicant to several patents of relevance to these beta glucans.Footnotes* This version of the manuscript has been revised to update the following: New Data included on evaluation of Dystrophin and IGF-1