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

Autor: Soraya Manaviazar, Sara Mata López, Karl J. Hale, Peter P. Nghiem, Hamish A. Watson, Madison Feng
Rok vydání: 2021
Předmět:
Popis: (-)-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
Databáze: OpenAIRE