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Myostatin inhibition with orally administered Lactobacillus casei expressing a modified human myostatin protein: functional benefits and translational potential in advanced Duchenne muscular dystrophy

Year: 2026

Type: article

Abstract: Background Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder that requires novel therapeutic approaches beyond dystrophin restoration. Myostatin, a negative regulator of muscle growth, has emerged as a promising target to enhance muscle mass and function. Methods We evaluated the efficacy of an orally administered Lactobacillus casei strain expressing a modified human myostatin protein (BLS-M22), in 32-week-old mdx mice. Animals received BLS-M22 or control ( L. casei -pgsA) for 8 weeks (control group = 8, treated group = 7) and 12 weeks (control group = 8, treated group = 9). Results BLS-M22 elicited a robust systemic anti-myostatin antibody response and significantly reduced serum creatine kinase levels, indicating attenuated muscle damage. Treated mice showed improved endurance in rotarod performance. However, no significant differences were observed in body weight, muscle fiber cross-sectional area, or fibrosis, reflecting the limited regenerative capacity at an advanced disease stage. Conclusion This study demonstrates that myostatin inhibition with orally administered L. casei expressing a modified human myostatin protein confers functional benefits even in advanced DMD, while highlighting its therapeutic limitations without concomitant dystrophin restoration. As a cost-effective, non-invasive, and immunologically distinct platform, this system holds translational potential not only for DMD but also for broader applications in sarcopenia and metabolic disorders.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2025.1693484