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Anti-inflammatory drugs for Duchenne muscular dystrophy: focus on skeletal muscle-releasing factors

Authors Miyatake S, Shimizu-Motohashi Y, Takeda S, Aoki Y

Received 8 April 2016

Accepted for publication 26 May 2016

Published 30 August 2016 Volume 2016:10 Pages 2745—2758

DOI https://doi.org/10.2147/DDDT.S110163

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


Shouta Miyatake,1 Yuko Shimizu-Motohashi,2 Shin’ichi Takeda,1 Yoshitsugu Aoki1

1Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; 2Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan

Abstract: Duchenne muscular dystrophy (DMD), an incurable and a progressive muscle wasting disease, is caused by the absence of dystrophin protein, leading to recurrent muscle fiber damage during contraction. The inflammatory response to fiber damage is a compelling candidate mechanism for disease exacerbation. The only established pharmacological treatment for DMD is corticosteroids to suppress muscle inflammation, however this treatment is limited by its insufficient therapeutic efficacy and considerable side effects. Recent reports show the therapeutic potential of inhibiting or enhancing pro- or anti-inflammatory factors released from DMD skeletal muscles, resulting in significant recovery from muscle atrophy and dysfunction. We discuss and review the recent findings of DMD inflammation and opportunities for drug development targeting specific releasing factors from skeletal muscles. It has been speculated that nonsteroidal anti-inflammatory drugs targeting specific inflammatory factors are more effective and have less side effects for DMD compared with steroidal drugs. For example, calcium channels, reactive oxygen species, and nuclear factor-κB signaling factors are the most promising targets as master regulators of inflammatory response in DMD skeletal muscles. If they are combined with an oligonucleotide-based exon skipping therapy to restore dystrophin expression, the anti-inflammatory drug therapies may address the present therapeutic limitation of low efficiency for DMD.

Keywords: calcium channels, ryanodine receptor 1, exon skipping, NF-κB, myokine, ROS

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