Osteopontin (OPN) Downregulatory Alkaloid (-)-Agelastatin A Prevents Muscle Damage in a Mouse Model of Duchenne Muscular Dystrophy

Madison Feng, Sara Mata López, Soraya Manaviazar, Hamish A Watson, Karl J. Hale*, Peter P Nghiem*

*Corresponding author for this work

Research output: Other contribution

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Abstract

(-)-Agelastatin A (AA) in 1,2-propanediol (3-deoxy-DL-glycerol) elicits a dose-dependent decrease in OPN mRNA expression in canine Duchenne Muscular Dystrophy (DMD) myoblasts at doses ranging from 0.01 nM-30 nM. When intraperitoneally administered in the same vehicle to mdx mice at 2.5 mg/kg/day for two weeks, and at 1.5 mg/kg/day twice-weekly for two weeks, (-)-AA brings about a significant decrease in exercise-induced muscle damage through its attenuation of OPN expression. Because (-)-AA is known to downregulate OPN, this study confirms that the use of small molecule OPN downregulatory drugs can beneficially modify the phenotype in DMD animal models and potentially affected boys.
Original languageEnglish
TypePreprint
Media of outputPreprint Server
PublisherChemRxiv
Number of pages9
DOIs
Publication statusPublished - 16 Mar 2021

Keywords

  • Osteopontin, β-catenin, (-)-agelastatin A, Duchenne muscular dystrophy (DMD), canine myoblasts, mdx mice

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