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

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

doi:10.26434/chemrxiv.14210882v1

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

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

^*Corresponding author for this work

School of Chemistry and Chemical Engineering

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 language	English
Type	Preprint
Media of output	Preprint Server
Publisher	ChemRxiv
Number of pages	9
DOIs	https://doi.org/10.26434/chemrxiv.14210882v1
Publication status	Published - 16 Mar 2021

Keywords

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

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10.26434/chemrxiv.14210882v1Licence: Unspecified

Osteopontin (OPN) Downregulatory Alkaloid (-)-Agelastatin A Prevents Muscle Damage in a Mouse Model of Duchenne Muscular Dystrophy
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited
Other version, 394 KBLicence: CC BY-NC-ND

Further investigations into the mechanism of the o-directed free radical hydrostannation of alkyl and aryl acetylenes
Watson, H. (Author), Stevenson, P. (Supervisor) & Hale, K. (Supervisor), Jul 2022
Student thesis: Doctoral Thesis › Doctor of Philosophy

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

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.",

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

author = "L{\'o}pez, {Sara Mata} and Soraya Manaviazar and Watson, {Hamish A} and Hale, {Karl J.} and Nghiem, {Peter P} and {Madison Feng}",

year = "2021",

month = mar,

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doi = "10.26434/chemrxiv.14210882v1",

language = "English",

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T1 - Osteopontin (OPN) Downregulatory Alkaloid (-)-Agelastatin A Prevents Muscle Damage in a Mouse Model of Duchenne Muscular Dystrophy

AU - López, Sara Mata

AU - Manaviazar, Soraya

AU - Watson, Hamish A

AU - Hale, Karl J.

AU - Nghiem, Peter P

AU - Madison Feng

PY - 2021/3/16

Y1 - 2021/3/16

N2 - (-)-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.

AB - (-)-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.

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

U2 - 10.26434/chemrxiv.14210882v1

DO - 10.26434/chemrxiv.14210882v1

M3 - Other contribution

PB - ChemRxiv

ER -

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

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Student theses

Further investigations into the mechanism of the o-directed free radical hydrostannation of alkyl and aryl acetylenes

Cite this