Age-progressive stratification of Becker muscular dystrophy patients: a focus on muscle biopsy fibrosis, inflammation and capillary network

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Skeletal muscle dystrophies comprise a group of inherited disorders characterized by progressive muscle weakness, with Duchenne and Becker muscular dystrophies (DMD/BMD) being among the most severe. These dystrophies are caused by mutations in the dystrophin gene, resulting in muscle cell instability, chronic inflammation, fibrosis, and impaired muscle regeneration. Although skeletal muscle has intrinsic regenerative potential via satellite cells, the ongoing muscle damage in DMD/BMD depletes these cells and promotes fibrosis. Inflammation also plays a pivotal role, with immune cell infiltration correlating with disease severity. This study investigates fibrosis, inflammation, and capillarization in BMD patients across different age groups to clarify how disease progression varies over time. Morphological analyses of muscle biopsies revealed an increase in connective tissue, particularly in adult patients. Pediatric patients showed reduced capillarization, whereas adult patients displayed vascular adaptations, including elevated capillary-to-fibre ratios and capillary contacts, indicative of compensatory mechanisms in response to chronic muscle degeneration. Inflammatory profiles also varied with age: younger adult patients exhibited a predominance of CD68-positive macrophages, while older adults demonstrated increased CD4/CD8 T-cell activity. Our findings highlight pronounced age-dependent differences in muscle pathology, encompassing structural adaptations, fibrosis, and inflammation, which may be crucial for developing age-tailored therapeutic approaches. • Our findings highlight age-specific differences in muscle pathology and immune responses in BMD. • Increased fibrosis, adipose tissue deposition, and regenerating fibres were seen in all BMD patients. • Capillary remodeling showed higher density in adults and reduced presence in pediatric BMD. • Inflammatory profile varied with age, showing macrophage and T-cell involvement in BMD. • Fibrosis correlated with CD206+ macrophages, suggesting their role in disease progression.

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