Mineralocorticoid Receptor Antagonists in Muscular Dystrophy Mice During Aging and Exercise

Journal of Neuromuscular Diseases
Jeovanna LowePaul M L Janssen

Abstract

Mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors have shown preclinical efficacy for both skeletal and cardiac muscle outcomes in young sedentary dystrophin-deficient mdx mice also haploinsufficient for utrophin, a Duchenne muscular dystrophy (DMD) model. The mdx genotypic DMD model has mild pathology, making non-curative therapeutic effects difficult to distinguish at baseline. Since the cardiac benefit of mineralocorticoid receptor antagonists has been translated to DMD patients, it is important to optimize potential advantages for skeletal muscle by further defining efficacy parameters. We aimed to test whether therapeutic effects of mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors are detectable using three different reported methods of exacerbating the mdx phenotype. We tested treatment with lisinopril and the mineralocorticoid receptor antagonist spironolactone in: 10 week-old exercised, 1 year-old sedentary, and 5 month-old isoproterenol treated mdx mice and performed comprehensive functional and histological measurements. None of the protocols to exacerbate mdx phenotypes resulted in dramatically enhanced pathology and no significant benefit...Continue Reading

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Citations

Nov 19, 2019·Frontiers in Physiology·J Spencer HauckJill A Rafael-Fortney
Jan 6, 2021·International Journal of Molecular Sciences·Moises Rodriguez-GonzalezAna Castellano-Martinez
Mar 6, 2021·Orphanet Journal of Rare Diseases·Stephanie KourakisEmma Rybalka

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