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Adenylosuccinic acid therapy ameliorates murine Duchenne Muscular Dystrophy

Citation

Timpani, CA and Goodman, CA and Stathis, CG and White, JD and Mamchaoui, K and Butler-Browne, G and Gueven, N and Hayes, A and Rybalka, E, Adenylosuccinic acid therapy ameliorates murine Duchenne Muscular Dystrophy, Scientific reports, 10, (1) Article 1125. ISSN 2045-2322 (2020) [Refereed Article]


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Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/s41598-020-57610-w

Abstract

Arising from the ablation of the cytoskeletal protein dystrophin, Duchenne Muscular Dystrophy (DMD) is a debilitating and fatal skeletal muscle wasting disease underpinned by metabolic insufficiency. The inability to facilitate adequate energy production may impede calcium (Ca2+) buffering within, and the regenerative capacity of, dystrophic muscle. Therefore, increasing the metabogenic potential could represent an effective treatment avenue. The aim of our study was to determine the efficacy of adenylosuccinic acid (ASA), a purine nucleotide cycle metabolite, to stimulate metabolism and buffer skeletal muscle damage in the mdx mouse model of DMD. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were treated with ASA (3000 g.mL-1) in drinking water. Following the 8-week treatment period, metabolism, mitochondrial density, viability and superoxide (O2-) production, as well as skeletal muscle histopathology, were assessed. ASA treatment significantly improved the histopathological features of murine DMD by reducing damage area, the number of centronucleated fibres, lipid accumulation, connective tissue infiltration and Ca2+ content of mdx tibialis anterior. These effects were independent of upregulated utrophin expression in the tibialis anterior. ASA treatment also increased mitochondrial viability in mdx flexor digitorum brevis fibres and concomitantly reduced O2- production, an effect that was also observed in cultured immortalised human DMD myoblasts. Our data indicates that ASA has a protective effect on mdx skeletal muscles.

Item Details

Item Type:Refereed Article
Keywords:Duchenne Muscular Dystrophy, Adenylosuccinic acid
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmaceutical Sciences
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
UTAS Author:Gueven, N (Dr Nuri Guven)
ID Code:137232
Year Published:2020
Deposited By:Pharmacy
Deposited On:2020-02-05
Last Modified:2020-05-26
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