Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Muscular Dystrophy: From Molecular Basis to Therapies

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 25876

Share This Special Issue

Special Issue Editor

Dr. Atsushi Asakura

E-Mail Website
Guest Editor

Paul & Sheila Wellstone Muscular Dystrophy Center, Department of Neurology, Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA
Interests: muscular dystrophy; satellite cell; gene therapy; exon skipping; muscle regeneration; iPSC; dystrophin; skeletal muscle
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and an X-linked progressive muscle wasting disease. DMD is caused by mutation in dystrophin. Dystrophin protein is essential to form the dystrophin-associated glycoprotein complex (DGC) at the sarcolemma, linking the muscle sarcomere to the extracellular matrix. Absence of functional dystrophin results in vulnerable muscle fibers to mechanical stretch. Currently, there is no definitive cure for DMD. Since the responsible gene has been identified for more than thirty years, translational researches have produced several clinically relevant results, which will be potential therapeutic ways for DMD. In this Special Issue (Muscular Dystrophy), we will discuss the current progress of therapeutic approaches for DMD, including gene therapy and cell therapy, as well as the fields of muscle regenerative medicine related to DMD research.

Assoc. Prof. Atsushi Asakura
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

muscular dystrophy
dystrophin
satellite cell
gene therapy
exon skipping
vascular therapy
regenerative medicine
skeletal muscle
muscle regeneration
iPSC

Published Papers (5 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

9 pages, 1368 KiB

Open AccessCommunication

Conditional Deletion of Dicer in Adult Mice Impairs Skeletal Muscle Regeneration

by Satoshi Oikawa, Minjung Lee and Takayuki Akimoto

Int. J. Mol. Sci. 2019, 20(22), 5686; https://doi.org/10.3390/ijms20225686 - 13 Nov 2019

Cited by 13 | Viewed by 3375

Abstract

Skeletal muscle has a remarkable regenerative capacity, which is orchestrated by multiple processes, including the proliferation, fusion, and differentiation of the resident stem cells in muscle. MicroRNAs (miRNAs) are small noncoding RNAs that mediate the translational repression or degradation of mRNA to regulate diverse biological functions. Previous studies have suggested that several miRNAs play important roles in myoblast proliferation and differentiation in vitro. However, their potential roles in skeletal muscle regeneration in vivo have not been fully established. In this study, we generated a mouse in which the Dicer gene, which encodes an enzyme essential in miRNA processing, was knocked out in a tamoxifen-inducible way (iDicer KO mouse) and determined its regenerative potential after cardiotoxin-induced acute muscle injury. Dicer mRNA expression was significantly reduced in the tibialis anterior muscle of the iDicer KO mice, whereas the expression of muscle-enriched miRNAs was only slightly reduced in the Dicer-deficient muscles. After cardiotoxin injection, the iDicer KO mice showed impaired muscle regeneration. We also demonstrated that the number of PAX7⁺ cells, cell proliferation, and the myogenic differentiation capacity of the primary myoblasts did not differ between the wild-type and the iDicer KO mice. Taken together, these data demonstrate that Dicer is a critical factor for muscle regeneration in vivo. Full article

(This article belongs to the Special Issue Muscular Dystrophy: From Molecular Basis to Therapies)

► Show Figures

Figure 1

11 pages, 5828 KiB

Open AccessCommunication

Human Skeletal Muscle Cells Derived from the Orbicularis Oculi Have Regenerative Capacity for Duchenne Muscular Dystrophy

by Yukito Yamanaka, Nana Takenaka, Hidetoshi Sakurai, Morio Ueno, Shigeru Kinoshita, Chie Sotozono and Takahiko Sato

Int. J. Mol. Sci. 2019, 20(14), 3456; https://doi.org/10.3390/ijms20143456 - 14 Jul 2019

Cited by 6 | Viewed by 3369

Abstract

Skeletal muscle stem cells (MuSCs) have been proposed as suitable candidates for cell therapy in muscular disorders since they exhibit good capacity for myogenic regeneration. However, for better therapeutic outcomes, it is necessary to isolate human MuSCs from a suitable tissue source with high myogenic differentiation. In this context, we isolated CD56+CD82+ cells from the extra eyelid tissue of young and aged patients, and tested in vitro myogenic differentiation potential. In the current study, myogenic cells derived from extra eyelid tissue were characterized and compared with immortalized human myogenic cells. We found that myogenic cells derived from extra eyelid tissue proliferated and differentiated myofibers in vitro, and restored DYSTROPHIN or PAX7 expression after transplantation with these cells in mice with Duchenne muscular dystrophy. Thus, human myogenic cells derived from extra eyelid tissue including the orbicularis oculi might be good candidates for stem cell-based therapies for treating muscular diseases. Full article

(This article belongs to the Special Issue Muscular Dystrophy: From Molecular Basis to Therapies)

► Show Figures

Figure 1

11 pages, 17130 KiB

Open AccessArticle

Expression and Functional Analyses of Dlk1 in Muscle Stem Cells and Mesenchymal Progenitors during Muscle Regeneration

by Lidan Zhang, Akiyoshi Uezumi, Takayuki Kaji, Kazutake Tsujikawa, Ditte Caroline Andersen, Charlotte Harken Jensen and So-ichiro Fukada

Int. J. Mol. Sci. 2019, 20(13), 3269; https://doi.org/10.3390/ijms20133269 - 03 Jul 2019

Cited by 10 | Viewed by 4037

Abstract

Delta like non-canonical Notch ligand 1 (Dlk1) is a paternally expressed gene which is also known as preadipocyte factor 1 (Pref−1). The accumulation of adipocytes and expression of Dlk1 in regenerating muscle suggests a correlation between fat accumulation and Dlk1 expression in the muscle. Additionally, mice overexpressing Dlk1 show increased muscle weight, while Dlk1-null mice exhibit decreased body weight and muscle mass, indicating that Dlk1 is a critical factor in regulating skeletal muscle mass during development. The muscle regeneration process shares some features with muscle development. However, the role of Dlk1 in regeneration processes remains controversial. Here, we show that mesenchymal progenitors also known as adipocyte progenitors exclusively express Dlk1 during muscle regeneration. Eliminating developmental effects, we used conditional depletion models to examine the specific roles of Dlk1 in muscle stem cells or mesenchymal progenitors. Unexpectedly, deletion of Dlk1 in neither the muscle stem cells nor the mesenchymal progenitors affected the regenerative ability of skeletal muscle. In addition, fat accumulation was not increased by the loss of Dlk1. Collectively, Dlk1 plays essential roles in muscle development, but does not greatly impact regeneration processes and adipogenic differentiation in adult skeletal muscle regeneration. Full article

(This article belongs to the Special Issue Muscular Dystrophy: From Molecular Basis to Therapies)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 337 KiB

Open AccessReview

Cardiac Pathophysiology and the Future of Cardiac Therapies in Duchenne Muscular Dystrophy

by Tatyana A. Meyers and DeWayne Townsend

Int. J. Mol. Sci. 2019, 20(17), 4098; https://doi.org/10.3390/ijms20174098 - 22 Aug 2019

Cited by 85 | Viewed by 10299

Abstract

Duchenne muscular dystrophy (DMD) is a devastating disease featuring skeletal muscle wasting, respiratory insufficiency, and cardiomyopathy. Historically, respiratory failure has been the leading cause of mortality in DMD, but recent improvements in symptomatic respiratory management have extended the life expectancy of DMD patients. With increased longevity, the clinical relevance of heart disease in DMD is growing, as virtually all DMD patients over 18 year of age display signs of cardiomyopathy. This review will focus on the pathophysiological basis of DMD in the heart and discuss the therapeutic approaches currently in use and those in development to treat dystrophic cardiomyopathy. The first section will describe the aspects of the DMD that result in the loss of cardiac tissue and accumulation of fibrosis. The second section will discuss cardiac small molecule therapies currently used to treat heart disease in DMD, with a focus on the evidence supporting the use of each drug in dystrophic patients. The final section will outline the strengths and limitations of approaches directed at correcting the genetic defect through dystrophin gene replacement, modification, or repair. There are several new and promising therapeutic approaches that may protect the dystrophic heart, but their limitations suggest that future management of dystrophic cardiomyopathy may benefit from combining gene-targeted therapies with small molecule therapies. Understanding the mechanistic basis of dystrophic heart disease and the effects of current and emerging therapies will be critical for their success in the treatment of patients with DMD. Full article

(This article belongs to the Special Issue Muscular Dystrophy: From Molecular Basis to Therapies)

► Show Figures

Graphical abstract

13 pages, 2134 KiB

Open AccessReview

Blockade of TRPV2 is a Novel Therapy for Cardiomyopathy in Muscular Dystrophy

by Yuko Iwata and Tsuyoshi Matsumura

Int. J. Mol. Sci. 2019, 20(16), 3844; https://doi.org/10.3390/ijms20163844 - 07 Aug 2019

Cited by 19 | Viewed by 4090

Abstract

Muscular dystrophy and dilated cardiomyopathy are intractable diseases and their treatment options are very limited. Transient receptor potential cation channel subfamily V, member 2 (TRPV2), is a stretch-sensitive Ca²⁺-permeable channel that causes sustained intracellular Ca²⁺ increase in muscular cells, which is a pathophysiological feature of degenerative muscular disease. Recent reports have clarified that TRPV2 is concentrated and activated in the sarcolemma of cardiomyocytes/myocytes during cardiomyopathy/heart failure and muscular dystrophy. Furthermore, these reports showed that inactivation of TRPV2 ameliorates muscle dysgenesis to improve cardiac function and survival prognosis. Although TRPV2 is a potential therapeutic target for cardiomyopathy, there were no TRPV2 inhibitors available until recently. In this review, we introduce our recent findings and discuss the current progress in the development of TRPV2 inhibitors and their therapeutic applications for cardiomyopathy associated with muscular dystrophy. Full article

(This article belongs to the Special Issue Muscular Dystrophy: From Molecular Basis to Therapies)

► Show Figures

Journal Menu

Journal Browser

Muscular Dystrophy: From Molecular Basis to Therapies

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (5 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI