INCREASED EXPRESSION OF HLA ABC CLASS I ANTIGENS BY MUSCLE FIBRES IN DUCHENNE MUSCULAR DYSTROPHY, INFLAMMATORY MYOPATHY, AND OTHER NEUROMUSCULAR DISORDERS

microRNAs (miRNAs) are small non-coding RNAs required for the post-transcriptional control of gene expression. MicroRNAs play a critical role in modulating muscle regeneration and stem cell behavior. Muscle regeneration is affected in muscular dystrophies, and a critical point for the development of effective strategies for treating muscle disorders is optimizing approaches to target muscle stem cells in order to increase the ability to regenerate lost tissue. Within this framework, miRNAs are emerging as implicated in muscle stem cell response in neuromuscular disorders and new methodologies to regulate the expression of key microRNAs are coming up. In this review, we summarize recent advances highlighting the potential of miRNAs to be used in conjunction with gene replacement therapies, in order to improve muscle regeneration in the context of Duchenne Muscular Dystrophy (DMD).

Download Full-text

N-CAM expression: The study of muscle disease in a tertiary center of Thailand

10.21203/rs.3.rs-27058/v1 ◽

2020 ◽

Author(s):

Kanyarat Laoyoung ◽

Jariya Waisayarat

Keyword(s):

Muscular Dystrophy ◽

Mitochondrial Myopathy ◽

Inflammatory Myopathy ◽

Clinical Information ◽

Muscle Disease ◽

P Value ◽

Muscle Fibres ◽

Pathological Findings ◽

Cell Surface Glycoprotein ◽

Tertiary Center

Abstract Background The neural cell adhesion molecule (N-CAM), also called CD56, is a cell-surface glycoprotein that mediates intercellular adhesive interactions in the nervous system. N-CAM is expressed in neuromuscular endplates, nerves, satellite cells, and embryonic muscle, but it is lost as development proceeds and is nearly absent from adult muscle. N-CAM re-expression was detected in a denervated, regenerating and degenerated muscle fibres. Muscle disease or myopathy is diagnosed based on the presence of denervated, regenerating and degenerated fibres on muscle biopsy combined with clinical information. Some regenerating fibres looked like normal fibre and were challenging to identify but showed positive N-CAM staining. Objectives To explore the expression of N-CAM in muscle disease. Methods N-CAM expression and interpretation were performed in a 3-year retrospective study of 75 muscle biopsies diagnosed with myopathies. The pathological findings and clinical information were also thoroughly reviewed. Results Of 75 myopathy patients, 41 (55%) cases were female, and 34 (45%) cases were male. The mean age was 35 years. The range of age was 3 months to 83 years. The expression of N-CAM and clinical information, including pathological findings, were analyzed using Fisher’s exact versus chi-square tests. N-CAM expression data was performed in 75 samples, 35 (46.67%) were positive for N-CAM, and 40 (53.33%) were negative for N-CAM. The diagnosis of the muscle disease was nonspecific myopathy with 35 (46%) cases, inflammatory myopathy with 17 (23%) cases, neurogenic myopathy with 9 (12%) cases, muscular dystrophy with 7 (9%) cases, non-diagnostic myopathy with 5 (7%) cases, and mitochondrial myopathy with 2 (3%) cases. The inflammatory myopathy showed positive N-CAM in 15 out of 17 cases with statistical significance (p-value < 0.001, ORs (95% CI) 14.250 (2.960-68.606)). N-CAM was also positive in muscular dystrophy, neurogenic myopathy, and nonspecific myopathy but was not statistically significant in p-value. No positive N-CAM was found in mitochondrial myopathy and non-diagnostic myopathy. Conclusion N-CAM expression accompanied by the pattern of staining could be considered to help narrow down the differential diagnosis of myopathies. We recommend further study in a larger group.

Download Full-text

Ankle-Foot Orthosis in Duchenne Muscular Dystrophy: A 4 year Experience in a Multidisciplinary Neuromuscular Disorders Clinic

The Indian Journal of Pediatrics ◽

10.1007/s12098-016-2251-7 ◽

2016 ◽

Vol 84 (3) ◽

pp. 211-215

Author(s):

Anupam Gupta ◽

Atchayaram Nalini ◽

Shanti Prakash Arya ◽

Seena Vengalil ◽

Meeka Khanna ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Neuromuscular Disorders ◽

Ankle Foot Orthosis ◽

Foot Orthosis

Download Full-text

Therapeutic Strategies for Duchenne Muscular Dystrophy: An Update

Genes ◽

10.3390/genes11080837 ◽

2020 ◽

Vol 11 (8) ◽

pp. 837 ◽

Cited By ~ 4

Author(s):

Chengmei Sun ◽

Luoan Shen ◽

Zheng Zhang ◽

Xin Xie

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Motor Neurons ◽

Neuromuscular Junctions ◽

Neuromuscular Disorders ◽

Dystrophin Gene ◽

Current Status ◽

Muscle Stem Cells ◽

Cell Based Therapy ◽

Dystrophin Protein

Neuromuscular disorders encompass a heterogeneous group of conditions that impair the function of muscles, motor neurons, peripheral nerves, and neuromuscular junctions. Being the most common and most severe type of muscular dystrophy, Duchenne muscular dystrophy (DMD), is caused by mutations in the X-linked dystrophin gene. Loss of dystrophin protein leads to recurrent myofiber damage, chronic inflammation, progressive fibrosis, and dysfunction of muscle stem cells. Over the last few years, there has been considerable development of diagnosis and therapeutics for DMD, but current treatments do not cure the disease. Here, we review the current status of DMD pathogenesis and therapy, focusing on mutational spectrum, diagnosis tools, clinical trials, and therapeutic approaches including dystrophin restoration, gene therapy, and myogenic cell transplantation. Furthermore, we present the clinical potential of advanced strategies combining gene editing, cell-based therapy with tissue engineering for the treatment of muscular dystrophy.

Download Full-text

The Duchenne muscular dystrophy gene and cancer

Cellular Oncology ◽

10.1007/s13402-020-00572-y ◽

2020 ◽

Author(s):

Leanne Jones ◽

Michael Naidoo ◽

Lee R. Machado ◽

Karen Anthony

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Muscle Protein ◽

Neuromuscular Disorders ◽

Becker Muscular Dystrophy ◽

Gene Products ◽

Large Gene ◽

Cancer Types ◽

And Function ◽

Dystrophin Protein

Abstract Background Mutation of the Duchenne muscular dystrophy (DMD) gene causes Duchenne and Becker muscular dystrophy, degenerative neuromuscular disorders that primarily affect voluntary muscles. However, increasing evidence implicates DMD in the development of all major cancer types. DMD is a large gene with 79 exons that codes for the essential muscle protein dystrophin. Alternative promotor usage drives the production of several additional dystrophin protein products with roles that extend beyond skeletal muscle. The importance and function(s) of these gene products outside of muscle are not well understood. Conclusions We highlight a clear role for DMD in the pathogenesis of several cancers, including sarcomas, leukaemia’s, lymphomas, nervous system tumours, melanomas and various carcinomas. We note that the normal balance of DMD gene products is often disrupted in cancer. The short dystrophin protein Dp71 is, for example, typically maintained in cancer whilst the full-length Dp427 gene product, a likely tumour suppressor, is frequently inactivated in cancer due to a recurrent loss of 5’ exons. Therefore, the ratio of short and long gene products may be important in tumorigenesis. In this review, we summarise the tumours in which DMD is implicated and provide a hypothesis for possible mechanisms of tumorigenesis, although the question of cause or effect may remain. We hope to stimulate further study into the potential role of DMD gene products in cancer and the development of novel therapeutics that target DMD.

Download Full-text

Corrigendum to “Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy” [Neuromuscular Disorders 26/9 (2016) 576–583]

Neuromuscular Disorders ◽

10.1016/j.nmd.2017.01.004 ◽

2017 ◽

Vol 27 (5) ◽

pp. e1

Author(s):

Eugenio Mercuri ◽

James Edward Signorovitch ◽

Elyse Swallow ◽

Jinlin Song ◽

Susan J. Ward

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Natural History ◽

Neuromuscular Disorders ◽

Walk Distance ◽

Minute Walk Distance ◽

Minute Walk

Download Full-text

Localization and characterization of dystrophin in muscle biopsy specimens from Duchenne muscular dystrophy and various neuromuscular disorders

Muscle & Nerve ◽

10.1002/mus.880121209 ◽

1989 ◽

Vol 12 (12) ◽

pp. 1009-1016 ◽

Cited By ~ 29

Author(s):

Makoto Uchino ◽

Shukuro Araki ◽

Teruhisa Miike ◽

Hitoo Teramoto ◽

Tetsuji Nakamura ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Muscle Biopsy ◽

Neuromuscular Disorders ◽

Biopsy Specimens

Download Full-text

Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy

Cells ◽

10.3390/cells9051119 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1119

Author(s):

Aleksandra Klimczak ◽

Agnieszka Zimna ◽

Agnieszka Malcher ◽

Urszula Kozlowska ◽

Katarzyna Futoma ◽

...

Keyword(s):

Skeletal Muscle ◽

Bone Marrow ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Progenitor Cells ◽

Muscle Function ◽

Progenitor Cell ◽

Genetic Disorder ◽

Cell Populations ◽

Muscle Fibres

Duchenne muscular dystrophy (DMD) is a genetic disorder associated with a progressive deficiency of dystrophin that leads to skeletal muscle degeneration. In this study, we tested the hypothesis that a co-transplantation of two stem/progenitor cell populations, namely bone marrow-derived mesenchymal stem cells (BM-MSCs) and skeletal muscle-derived stem/progenitor cells (SM-SPCs), directly into the dystrophic muscle can improve the skeletal muscle function of DMD patients. Three patients diagnosed with DMD, confirmed by the dystrophin gene mutation, were enrolled into a study approved by the local Bioethics Committee (no. 79/2015). Stem/progenitor cells collected from bone marrow and skeletal muscles of related healthy donors, based on HLA matched antigens, were expanded in a closed MC3 cell culture system. A simultaneous co-transplantation of BM-MSCs and SM-SPCs was performed directly into the biceps brachii (two patients) and gastrocnemius (one patient). During a six-month follow-up, the patients were examined with electromyography (EMG) and monitored for blood kinase creatine level. Muscle biopsies were examined with histology and assessed for dystrophin at the mRNA and protein level. A panel of 27 cytokines was analysed with multiplex ELISA. We did not observe any adverse effects after the intramuscular administration of cells. The efficacy of BM-MSC and SM-SPC application was confirmed through an EMG assessment by an increase in motor unit parameters, especially in terms of duration, amplitude range, area, and size index. The beneficial effect of cellular therapy was confirmed by a decrease in creatine kinase levels and a normalised profile of pro-inflammatory cytokines. BM-MSCs may support the pro-regenerative potential of SM-SPCs thanks to their trophic, paracrine, and immunomodulatory activity. Both applied cell populations may fuse with degenerating skeletal muscle fibres in situ, facilitating skeletal muscle recovery. However, further studies are required to optimise the dose and timing of stem/progenitor cell delivery.

Download Full-text