(-)-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.
- Osteopontin, β-catenin, (-)-agelastatin A, Duchenne muscular dystrophy (DMD), canine myoblasts, mdx mice
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Further investigations into the mechanism of the o-directed free radical hydrostannation of alkyl and aryl acetylenesAuthor: Watson, H., Jul 2022
Supervisor: Stevenson, P. (Supervisor) & Hale, K. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy