Investigating the Compatibility of Weekly Prednisone with Daily Finerenone in Duchenne Muscular Dystrophy Mouse Models
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Date
2025-05
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The Ohio State University
Abstract
Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin gene, leading to progressive skeletal muscle degeneration, cardiomyopathy, and fibrosis. Glucocorticoids, such as prednisone, are the standard-of-care for managing DMD due to their anti-inflammatory effects, but long-term use is associated with significant side effects and may exacerbate cardiac and skeletal muscle pathology. Mineralocorticoid receptor antagonists (MRAs), including finerenone, have demonstrated promise in reducing fibrosis and improving muscle function in dystrophic models. However, glucocorticoids and MRAs share overlapping receptor interactions, potentially diminishing the efficacy of MRAs when administered concurrently. This study aimed to determine whether a clinical compromise—using weekly prednisone in combination with daily finerenone—could preserve the anti-inflammatory benefits of glucocorticoids while maximizing the anti-fibrotic effects of MRAs. A short-term study using mdx mice and a long-term 16-week study using het mice were conducted. Mice were treated with either daily prednisone, daily finerenone, or a combination of weekly prednisone and daily finerenone. Muscle damage, fibrosis, and inflammatory cell infiltration were assessed using immunofluorescence staining for IgG, fibronectin, CD11b, and matrix Gla protein (MGP).
Results demonstrated that daily finerenone significantly reduced muscle damage compared to prednisone, with lower IgG staining in quadriceps muscles. In contrast, the combination of prednisone and finerenone did not reduce fibrosis or muscle damage in long-term studies, and in some cases exacerbated pathology. MGP expression was selectively upregulated by glucocorticoids, suggesting GR-dependent regulation, rather than MR-specific signaling. These findings highlight the complexity of combining glucocorticoids and MRAs in DMD therapy. While finerenone alone improves muscle pathology, its benefits may be diminished when co-administered with glucocorticoids. Future studies should investigate modified MRAs or alternative dosing regimens to optimize combination treatment strategies for DMD.
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Keywords
Duchenne Muscular Dystrophy, Glucocorticoids, Fibrosis, Prednisone