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Osteopontin (OPN) Downregulatory Alkaloid (-)-Agelastatin A Prevents Muscle Damage in a Mouse Model of Duchenne Muscular Dystrophy.pdf (394.08 kB)

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

preprint
submitted on 12.03.2021, 21:35 and posted on 16.03.2021, 05:41 by Madison Feng, Sara Mata Lopez, Soraya Manaviazar, Hamish A. Watson, Karl Hale, Peter P Nghiem

(-)-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

Funding

Texas A & M Starter Grant

Department for the Economy (DfE) Northern Ireland Postgraduate Studentship

ACS Publications Grant

History

Email Address of Submitting Author

k.j.hale@qub.ac.uk

Institution

Queen's University Belfast

Country

Northern ireland, United Kingdom

ORCID For Submitting Author

0000-0002-6756-8763

Declaration of Conflict of Interest

No conflict of interest

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