Abstract

Limb-Girdle Muscular Dystrophy Type 2B/R2 (LGMD2B/R2) is a type of dysferlinopathy, a progressive muscle-wasting disorder caused by mutations in the dysferlin gene. Hallmarks of the disease include chronic inflammation, impaired muscle regeneration, and eventual muscle degeneration. Currently, no FDA-approved therapies are available for dysferlinopathies. Recombinant human Galectin-1 (rHsGal-1) has shown multiple roles in maintaining skeletal muscle homeostasis, promoting muscle repair, enhancing myogenesis, and modulating inflammation by downregulating the NF-ÎºB pathway. The ability of rHsGal-1 to modulate the immune response is particularly promising for therapeutic applications in patients with LGMD2B/R2. In this study, we evaluated the effects of rHsGal-1 in a dysferlin-deficient mouse model of LGMD2B/R2 (Bla/J), hypothesizing that it protects muscles from chronic pro-inflammatory M1 macrophage activation by promoting a shift towards anti-inflammatory M2 macrophages. Our results show that rHsGal-1 treatment significantly reduces the number of CD86+ pro-inflammatory macrophages and increases CD206+ anti-inflammatory macrophages in peritoneal exudate cells (PECs), both in-vitro and in-vivo. The increase in anti-inflammatory macrophages, which are associated with tissue repair and remodeling, was accompanied by changes in cytokine levels in serum, further indicating the potential of rHsGal-1 to mitigate inflammation. Histological analysis revealed improvements in muscle health, including reduced lipid infiltration, decreased centrally located nuclei (CLN), and increased myofiber diameter (MFD). These findings suggest that rHsGal-1 holds strong therapeutic potential for LGMD2B/R2 by reducing inflammation and enhancing muscle health.

Degree

College and Department

Chemistry and Biochemistry; Computational, Mathematical, and Physical Sciences

Rights

https://lib.byu.edu/about/copyright/