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Mol Ther 2019 Feb 12. Epub 2019 Feb 12.

MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.

Mol Ther Nucleic Acids 2019 Jan 25;14:520-535. Epub 2019 Jan 25.

Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan. Electronic address:

Exon skipping using phosphorodiamidate morpholino oligomers (PMOs) is a promising treatment strategy for Duchenne muscular dystrophy (DMD). The most significant limitation of these clinically used compounds is their lack of delivery systems that target muscles; thus, cell-penetrating peptides are being developed to enhance uptake into muscles. Recently, we reported that uptake of peptide-conjugated PMOs into myofibers was mediated by scavenger receptor class A (SR-A), which binds negatively charged ligands. Read More

J Card Fail 2019 Feb 11. Epub 2019 Feb 11.

Thomas P Graham Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN United States of America; Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN United States of America. Electronic address:

Background: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Read More

PLoS One 2019 14;14(2):e0212437. Epub 2019 Feb 14.

Musculoskeletal Science & Sports Medicine Research Centre, School of Healthcare Science, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, United Kingdom.

Introduction: The purpose of this study was to present and compare pain between adult males with Duchenne (DMD), Becker's (BMD), Limb-Girdle (LGMD) Facioscapulohumeral (FSHD) forms of Muscular Dystrophy (MD), and healthy controls (CTRL), using three different methods of assessment.

Methods: Pain was assessed using 1) a whole body visual analogue scale (VAS) of pain, 2) a generalised body map and 3) a localised body map.

Results: All types of MD reported more VAS pain than CTRL, with 97% of all MD participants reporting pain; however, no differences were reported between types of MD. Read More

Eur J Pediatr 2019 Feb 14. Epub 2019 Feb 14.

Developmental Endocrinology Research Group, Royal Hospital for Children, 1345 Govan Road, G51 4TF, Glasgow, UK.

We aimed to compare body segment and bone lengths in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD) with healthy controls using dual-energy absorptiometry (DXA) images. Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia) in boys with DMD and age-matched control boys were measured using DXA. Thirty boys with DMD (median age 10. Read More

Front Neurol 2019 29;10:24. Epub 2019 Jan 29.

Post-graduate Program in Rehabilitation Sciences, School of Medicine, University of São Paulo, São Paulo, Brazil.

There is a need to support individuals with Duchenne Muscular Dystrophy (DMD) to achieve optimal functionality in everyday life and with meaningful tasks and activities, throughout stages of the disease progression. Thus, technological developments have created an exciting opportunity for the use of affordable virtual reality (VR) systems with different kinds of interaction devices, providing an efficient and fun tool for enabling improvement in motor performance. To compare performance on a virtual task using interfaces with and without physical contact in order to identify functionality by using different devices in individuals with DMD. Read More

Sci Rep 2019 Feb 13;9(1):1986. Epub 2019 Feb 13.

Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Mitochondria play an important role in providing ATP for muscle contraction. Muscle physiology is compromised in Duchenne muscular dystrophy (DMD) and several studies have shown the involvement of bioenergetics. In this work we investigated the mitochondrial physiology in fibers from fast-twitch muscle (EDL) and slow-twitch muscle (soleus) in the mdx mouse model for DMD and in control C57BL/10J mice. Read More

Hum Mol Genet 2019 Feb 13. Epub 2019 Feb 13.

Department of Physiology and Cell Biology.

Mineralocorticoid receptor (MR) drugs have been used clinically for decades to treat cardiovascular diseases. MR antagonists show preclinical efficacy not only for heart in Duchenne muscular dystrophy models, but also improve skeletal muscle force and muscle membrane integrity. The mechanisms of action of MR antagonists in skeletal muscles are entirely unknown. Read More

Proc Natl Acad Sci U S A 2019 Feb 12. Epub 2019 Feb 12.

School of Biological Sciences, Illinois State University, Normal, IL 61790;

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. Read More

Life Sci Alliance 2019 Feb 11;2(1). Epub 2019 Feb 11.

Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Cardiomyopathy is a leading cause of death for Duchenne muscular dystrophy. Here, we find that the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) can share common ligands but play distinct roles in dystrophic heart and skeletal muscle pathophysiology. Comparisons of their ligand structures indicate that the Δ9,11 modification of the first-in-class drug vamorolone enables it to avoid interaction with a conserved receptor residue (N770/N564), which would otherwise activate transcription factor properties of both receptors. Read More

Neuromuscul Disord 2018 Nov 3. Epub 2018 Nov 3.

FCCP Internacional Fellow AARC, Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain.

J Clin Pharmacol 2019 Feb 11. Epub 2019 Feb 11.

Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.

Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder occurring in boys and caused by mutations in the dystrophin gene. Vamorolone is a first-generation delta-9,11 compound that has favorable efficacy and side effect profiles relative to classical glucocorticoids. The pharmacokinetics (PK) of oral vamorolone were assessed in parallel-group studies in healthy men (phase 1, n = 86) and boys with DMD (phase 2a, n = 48) during 14 days of once-daily dosing with a range of doses. Read More

Neuromuscul Disord 2018 Dec 8. Epub 2018 Dec 8.

U.O. Fisiopatologia Respiratoria, Azienda Ospedaliera di Padova, Via Giustiniani, 2, 35128 Padova, Italy.

Hum Genet 2019 Feb 7. Epub 2019 Feb 7.

Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 4458 TAMU, College Station, TX, 77843-4458, USA.

Therapies for Duchenne muscular dystrophy (DMD) must first be tested in animal models to determine proof-of-concept, efficacy, and importantly, safety. The murine and canine models for DMD are genetically homologous and most commonly used in pre-clinical testing. Although the mouse is a strong, proof-of-concept model, affected dogs show more analogous clinical and immunological disease progression compared to boys with DMD. Read More

Ther Adv Chronic Dis 2019 31;10:2040622318821622. Epub 2019 Jan 31.

Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Pneumologie, ORL & Dermatologie, Université Catholique de Louvain, Brussels, Belgium.

Background: The purpose of this systematic review was to summarize the different dysphagia screening and evaluation tools, and to identify their measurement properties in adults with neuromuscular diseases (NMDs).

Methods: A systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was conducted across three databases ( and ). Read More

Brain Dev 2019 Feb 2. Epub 2019 Feb 2.

Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Whole-exome sequencing (WES) can comprehensively detect both pathogenic single nucleotide variants and copy number variants, enabling identification of a coexistence of two or more genetic etiologies. Here we report a family consisting of individuals with Becker muscular dystrophy and rippling muscle disease. The proband, a 12-year-old boy, was diagnosed with Becker muscular dystrophy with exon 45-55 DMD deletions at age 4. Read More

J Magn Reson Imaging 2019 Feb 4. Epub 2019 Feb 4.

Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Background: Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disease leading to progressive muscle wasting. Since there is a need for MRI variables that serve as early sensitive indicators of response to treatment, several quantitative MRI methods have been suggested for disease monitoring.

Purpose: To evaluate the potential of sodium ( Na) and proton ( H) MRI methods to assess early pathological changes in skeletal muscle of DMD. Read More

Mol Ther 2019 Jan 25. Epub 2019 Jan 25.

Molecular and Cellular Biology Program, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA 98195, USA; Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address:

Gene therapies using adeno-associated viral (AAV) vectors have advanced into clinical trials for several diseases, including Duchenne muscular dystrophy (DMD). A limitation of AAV is the carrying capacity (∼5 kb) available for genes and regulatory cassettes (RCs). These size constraints are problematic for the 2. Read More

Bone 2019 Feb 1;121:232-242. Epub 2019 Feb 1.

Department of Pharmacology and Toxicology, University of Toronto, ON, Canada. Electronic address:

Duchenne Muscular Dystrophy (DMD) is a progressive muscle disorder caused by genetic mutations of the dystrophin encoding gene. In the absence of functional dystrophin, DMD patients suffer from muscle inflammation and wasting, as well as compromised bone health with increased risk of fracture. The use of high dose glucocorticoids (GC) as the standard therapy also contributes to bone fragility. Read More

Cell Stem Cell 2019 Jan 31. Epub 2019 Jan 31.

Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. Electronic address:

Loss of dystrophin expression in Duchenne muscular dystrophy (DMD) causes progressive degeneration of skeletal muscle, which is exacerbated by reduced self-renewing asymmetric divisions of muscle satellite cells. This, in turn, affects the production of myogenic precursors and impairs regeneration and suggests that increasing such divisions may be beneficial. Here, through a small-molecule screen, we identified epidermal growth factor receptor (EGFR) and Aurora kinase A (Aurka) as regulators of asymmetric satellite cell divisions. Read More

Brain Res Bull 2019 Jan 31. Epub 2019 Jan 31.

Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School Bari, University of Bari, Italy. Electronic address:

A fraction of patients affected by Duchenne muscular dystrophy (DMD) shows mental disability as a consequence of neuronal and metabolic alteration. In this study, we evaluated the effect of α-methyl-prednisolone (PDN) on the expression of the angiogenic marker HIF 1α, VEGF and VEGFR- 2 in correlation with PKC expression in the brain of mdx mouse, an experimental model of DMD. We demonstrated that HIF 1α, VEGF and VEGFR- 2 are overexpressed in the brain of dystrophic mdx mice in parallel with an increase of PKC expression and reduction of the tight junctions Occludin leading to altered angiogenesis. Read More

Mol Ther 2019 Jan 15. Epub 2019 Jan 15.

Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pediatrics, Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, OH 43210, USA. Electronic address:

Dilated cardiomyopathy is a common cause of death in patients with Duchenne muscular dystrophy (DMD). Gene therapies for DMD must, therefore, have a therapeutic impact in cardiac as well as skeletal muscles. Our previous studies have shown that GALGT2 overexpression in mdx skeletal muscles can prevent muscle damage. Read More

Muscle Nerve 2019 Feb 1. Epub 2019 Feb 1.

Department of Pediatrics, Nationwide Children's Hospital, Ohio State University, Columbus, Ohio, USA.

Introduction: Glucocorticosteroids (GC) are effective in slowing weakness in boys with Duchenne muscular dystrophy (DMD).

Methods: This is a multisite, one-year, open-label trial of twice-weekly prednisolone (5mg/kg/dose) in infants/young boys (0.4-2. Read More

Methods Mol Biol 2019 ;1937:281-294

Department of Veterinary Pathobiology, College of Veterinary Medicine, The University of Missouri, Columbia, MO, USA.

Many diseases affect multiple tissues and/or organ systems, or affect tissues that are broadly distributed. For these diseases, an effective gene therapy will require systemic delivery of the therapeutic vector to all affected locations. Adeno-associated virus (AAV) has been used as a gene therapy vector for decades in preclinical studies and human trials. Read More

Respir Care 2019 Feb;64(2):236-238

Scientific Institute IRCCS E. Medea Bosisio Parini, Lecco, Italy.

Respir Care 2019 Feb;64(2):235-236

Sleep and Breathing and NIHR Respiratory Biomedical Research Unit Royal Brompton & Harefield NHS Foundation Trust London, United Kingdom.

Int J Mol Sci 2019 Jan 30;20(3). Epub 2019 Jan 30.

Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy.

New scientific findings have recently shown that dasatinib (DAS), the first-choice oral drug in the treatment of chronic myeloid leukemia (CML) for adult patients who are resistant or intolerant to imatinib, is also potentially useful in the paediatric age. Moreover, recent preclinical evidences suggest that this drug could be useful for the treatment of Duchenne muscular dystrophy, since it targets cSrc tyrosin kinase. Based on these considerations, the purpose of this work was to use the strategy of complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) in order to obtain an aqueous preparation of DAS, which is characterized by a low water solubility (6. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Feb;36(2):151-153

Center of Genetics and Prenatal Diagnosis, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Objective: To explore the clinical features and genetic diagnosis of two cases with rare diseases and X chromosome abnormalities.

Methods: Multiple ligation-dependent probe amplification (MLPA) and karyotype analysis were carried out on an 8-year-old girl who was diagnosed with Duchenne muscular dystrophy. Karyotype analysis and PCR assay for SRY and AZF genes were carried out for a-2-month-old male infant with short penis. Read More

PLoS One 2019 30;14(1):e0211597. Epub 2019 Jan 30.

Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.

MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level. Several miRNAs are exclusively expressed in skeletal muscle and participate in the regulation of muscle differentiation by interacting with myogenic factors. These miRNAs can be found at high levels in the serum of patients and animal models for Duchenne muscular dystrophy, which is expected to be useful as biomarkers for their clinical conditions. Read More

PLoS One 2019 30;14(1):e0211384. Epub 2019 Jan 30.

Department of Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom.

The mdx mouse is the most widely-used animal model of the human disease Duchenne muscular dystrophy, and quantitative PCR analysis of gene expression in the muscles of this animal plays a key role in the study of pathogenesis and disease progression and in evaluation of potential therapeutic interventions. Normalization to appropriate stably-expressed reference genes is essential for accurate quantitative measurement, but determination of such genes is challenging: healthy and dystrophic muscles present very different transcriptional environments, further altering with disease progression and muscle use, raising the possibility that no single gene or combination of genes may be stable under all experimental comparative scenarios. Despite the pedigree of this animal model, this problem remains unaddressed. Read More

Muscle Nerve 2019 Jan 30. Epub 2019 Jan 30.

Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA, 55455.

Introduction: The vasculature and blood flow in muscle is perturbed in Duchenne muscular dystrophy (DMD) and its mdx mouse model. MicroRNA-92a (miR-92a) is enriched in endothelial cells, especially during ischemic injury.

Methods: Since antagonizing miR-92a was shown to result in increased proliferation and migration of endothelial cells and recovery from ischemia, we assessed the effects of Antagomir-92a in vitro in muscle stem cell culture and in vivo in mdx mice. Read More

Int J Yoga 2019 Jan-Apr;12(1):55-61

Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.

Background: Duchene muscular dystrophy (DMD) is a progressive muscular disorder. Cardiac disorder is the second-most common cause of death in children with DMD, with 10%-20% of them dying of cardiac failure. Heart rate variability (HRV) is shown to be a predictor of cardio-autonomic function. Read More

Cell Death Dis 2019 Jan 28;10(2):82. Epub 2019 Jan 28.

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Duchenne muscular dystrophy (DMD) is a progressive, lethal, X-linked disease of skeletal and cardiac muscles caused by mutations in the dystrophin gene. Loss of dystrophin leads to muscle fiber damage and impairment of satellite cell asymmetric division, which are essential for muscle regeneration. These processes ultimately result in muscle wasting and the replacement of the degenerating muscles by fibrogenic cells, a process that leads to the generation of fibrotic tissues. Read More

Hum Mol Genet 2019 Jan 28. Epub 2019 Jan 28.

Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX.

The dystrophin-/-/utrophin-/- double knockout (dKO-Hom) mouse is a murine model of human Duchenne muscular dystrophy (DMD). This study investigated the bone and muscle abnormalities of dKO-Hom mouse and mechanisms. We collected bone and skeletal muscle samples from control mice and three muscular dystrophic mouse models at different ages, and performed MicroCT and histological analyses of both bone and skeletal muscle tissues. Read More

Mol Neurobiol 2019 Jan 28. Epub 2019 Jan 28.

Centro de Envejecimiento y Regeneración, CARE Chile UC, Pontificia Universidad Católica de Chile, Santiago, Chile.

Connective tissue growth factor (CTGF/CCN2) is a matricellular protein that belongs to the CCN family of proteins. Since its discovery, it has been linked to cellular processes such as cell proliferation, differentiation, adhesion, migration, and synthesis of extracellular matrix (ECM) components, among others. The pro-fibrotic role of CTGF/CCN2 has been well-studied in several pathologies characterized by the development of fibrosis. Read More

J Vis Exp 2019 Jan 12(143). Epub 2019 Jan 12.

Division of Pediatric Neurology, University Children's Hospital Basel (UKBB), University of Basel; Department of Neurology, University Hospital Basel, University of Basel; Division of Neurology, University Clinic of Medicine, Cantonal Hospital Baselland, Bruderholz.

While the number of new treatment options tested in patients with Duchenne muscular dystrophy (DMD) is increasing, there is still no defining of the most reliable assessments regarding therapeutic efficacy. We present clinical and radiological outcome measures used in ambulatory patients participating in our trial "Treatment with L-citrulline and metformin in Duchenne muscular dystrophy". The motor function measure is a validated test in patients with neuromuscular disorders that consists of 32 items and assesses all three dimensions of motor performance including standing and transfer (D1 subscore), axial and proximal motor function (D2 subscore), and distal motor function (D3 subscore). Read More

Neurol Int 2018 Dec 20;10(4):7917. Epub 2018 Dec 20.

Service of Medical Resuscitation, Home Ventilation Unit, Raymond Poincaré, University of Versailles Saint Quentin en Yvelines, Garches.

Heart failure and restrictive respiratory insufficiency are complications in muscular dystrophies. We aimed to assess the accuracy of the B-natriuretic peptide (BNP) for the diagnosis of decompensated heart failure in muscular dystrophy. We included patients with muscular dystrophy and chronic respiratory insufficiency admitted in the Intensive Care Unit of the Raymond Poincare hospital (Garches, France) for suspected decompensated heart failure. Read More

Int J Cardiol 2019 Jan 17. Epub 2019 Jan 17.

Department of Pediatric Cardiology and Cardiac Surgery, Cardiology Unit, Bambino Gesù Hospital & Research Institute, Rome, Italy.

Background: End-stage dilated cardiomyopathy (DCM) is the leading cause of morbidity and mortality in patients with Duchenne Muscular Dystrophy (DMD). No studies are available on the effect of ivabradine on long-term outcomes in end-stage DMD/DCM.

Methods: We prospectively enrolled a cohort of end-stage DMD/DCM patients with LV ejection fraction <40%, on chronic HF treatment with an ACE inhibitor referred consecutively from 2012 to 2017 to Bambino Gesù Children's Hospital. Read More

Biochim Biophys Acta Mol Basis Dis 2019 Jan 24. Epub 2019 Jan 24.

Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland. Electronic address:

Pathophysiology of Duchenne Muscular Dystrophy (DMD) is still elusive. Although progressive wasting of muscle fibres is a cause of muscle deterioration, there is a growing body of evidence that the triggering effects of DMD mutation are present at the earlier stage of muscle development and affect myogenic cells. Among these abnormalities, elevated activity of P2X7 receptors and increased store-operated calcium entry myoblasts have been identified in mdx mouse. Read More

Cardiol Young 2019 Jan 26:1-7. Epub 2019 Jan 26.

1Thomas P Graham Division of Pediatric Cardiology,Department of Pediatrics,Vanderbilt University Medical Center,Nashville,TN,USA.

Background: Outcome analyses in large administrative databases are ideal for rare diseases such as Becker and Duchenne muscular dystrophy. Unfortunately, Becker and Duchenne do not yet have specific International Classification of Disease-9/-10 codes. We hypothesised that an algorithm could accurately identify these patients within administrative data and improve assessment of cardiovascular morbidity. Read More

J Am Soc Echocardiogr 2019 Jan 21. Epub 2019 Jan 21.

PHYMEDEXP, University of Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France.

Background: Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Speckle-tracking echocardiographic (STE) imaging is emerging as a noninvasive functional biomarker to consider in the early detection of DMD-related cardiomyopathy. However, STE analysis has not been assessed in a prospectively controlled study, especially in presymptomatic children with DMD, and no study has used STE analysis in all three displacements (longitudinal, radial, and circumferential) and for both ventricles. Read More

Respiration 2019 Jan 24:1-12. Epub 2019 Jan 24.

Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), Section of Anesthesia, Analgesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, University of Palermo, Palermo, Italy.

Background: Noninvasive mechanical ventilation (NIV) is an effective treatment in patients with neuromuscular diseases (NMD) to improve symptoms, quality of life, and survival.

Summary: NIV should be used early in the course of respiratory muscle involvement in NMD patients and its requirements may increase over time. Therefore, training on technical equipment at home and advice on problem solving are warranted. Read More

Neurology 2019 Jan 23. Epub 2019 Jan 23.

From The Heart Institute (M.T., J.J., B.G.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics and Molecular Genetics and Microbiology, Powell Gene Therapy Center (B.B.), and Division of Pediatric Cardiology, Congenital Heart Center (J.F.), University of Florida, Gainesville; Department of Cardiology (J.L., B.A.-V., M.R.O.), Johns Hopkins University, Baltimore, MD; Smidt Heart Institute (R.M., E.M., R.G.V.), Cedars-Sinai Medical Center, Los Angeles, CA; Capricor Therapeutics (R.R.S., B.F., J.R., J.M.P., L.M., D.D.A.), Beverly Hills, CA; and Department of Cardiology (K.M.), Laikon Hospital, Athens, Greece.

Objective: To assess the feasibility, safety, and efficacy of intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients with Duchenne muscular dystrophy (DMD).

Methods: The Halt Cardiomyopathy Progression (HOPE)-Duchenne trial is a phase I/II, randomized, controlled, open-label trial (NCT02485938). Patients with DMD >12 years old, with substantial myocardial fibrosis, were randomized (1:1) to usual care (control) or global intracoronary infusion of CAP-1002 (75 million cells). Read More

J Physiol 2019 Jan 23. Epub 2019 Jan 23.

School of Kinesiology and Health Science and the Muscle Health Research Centre, York University, Toronto, ON, Canada.

KEY POINTS SUMMARY: -98% of patients with Duchenne muscular dystrophy (DMD) develop cardiomyopathy, with 40% developing heart failure -While increased propensity for mitochondrial induction of cell death has been observed in left ventricle, it remains unknown whether this is linked to impaired mitochondrial respiratory control and elevated H O emission prior to the onset of cardiomyopathy -Classic mouse models of DMD demonstrate hyper-regeneration in skeletal muscle which may mask mitochondrial abnormalities. Using a model with less regenerative capacities that is more akin to DMD patients, we observed elevated left ventricular mitochondrial H O and impaired oxidative phosphorylation in the absence of cardiac remodelling or overt cardiac dysfunction at 4 weeks -These impairments were associated with dysfunctions at Complex I, governance by ADP and creatine-dependent phosphate shuttling which results in a less efficient response to energy demands -Mitochondria may be a therapeutic target for the treatment of cardiomyopathy in DMD ABSTRACT: In Duchenne muscular dystrophy (DMD), mitochondrial dysfunction is predicted as a response to numerous cellular stressors yet the degree and contribution of mitochondria to the onset of cardiomyopathy remains unknown. To resolve this uncertainty, we designed in vitro assessments of mitochondrial bioenergetics to model mitochondrial control parameters that influence cardiac function. Read More

Nucleic Acid Ther 2019 Jan 23. Epub 2019 Jan 23.

1 Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.

Duchenne muscular dystrophy is a severe, progressive muscle-wasting disease that is caused by mutations that abolish the production of functional dystrophin protein. The exon skipping approach aims to restore the disrupted dystrophin reading frame, to allow the production of partially functional dystrophins, such as found in the less severe Becker muscular dystrophy. Exon skipping is achieved by antisense oligonucleotides (AONs). Read More

J Mol Cell Cardiol 2019 Jan 19;128:51-61. Epub 2019 Jan 19.

Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN, USA; Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN, USA. Electronic address:

Background: Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by skeletal muscle degeneration and a significant cardiomyopathy secondary to cardiomyocyte damage and myocardial loss. The molecular basis of DMD lies in the absence of the protein dystrophin, which plays critical roles in mechanical membrane integrity and protein localization at the sarcolemma. A popular mouse model of DMD is the mdx mouse, which lacks dystrophin and displays mild cardiac and skeletal pathology that can be exacerbated to advance the disease state. Read More

Respir Physiol Neurobiol 2019 Jan 17;262:1-11. Epub 2019 Jan 17.

Department of Pediatrics, School of Medical Sciences, University of Campinas, 13081-970, P.O. Box: 6111 Campinas, São Paulo, Brazil; Laboratory of Pulmonary Physiology, Center for Pediatrics Investigation, School of Medical Sciences, University of Campinas, 13081-970, P.O. Box: 6111 Campinas, São Paulo, Brazil. Electronic address:

Introduction: Duchenne muscular dystrophy(DMD) shows motor and respiratory impairment.

Methods: 19 DMD patients (DMDG) (nine ambulatory and 10 non-ambulatory) were evaluated through motor function measure (MFM), 6-minute walk test (6MWT), respiratory muscle strength, cough peak flow, spirometry and volumetric capnography (VCap) tools. Control group that performed spirometry and VCap (CG1-n = 17) were different from those that performed the 6MWT (CG2-n = 8). Read More

Clin Chim Acta 2019 Jan 17;491:66-73. Epub 2019 Jan 17.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China. Electronic address:

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive, inherited neuromuscular disorders, caused by pathogenic variants in the dystrophin gene that encodes the dystrophin protein. A number of mutations have been identified in the past years, producing dystrophin diversity and resulting in mild to severe phenotypes in patients. Mutations in the dystrophin gene can be characterized by laboratory testing to confirm a clinical diagnosis of DMD/BMD. Read More

Cells 2019 Jan 15;8(1). Epub 2019 Jan 15.

Department of Biology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic.

Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor's involvement in the disease pathology often leading to the DMD patient's death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. Read More

Cell Rep 2019 Jan;26(3):689-701.e6

Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:

Most human cancers originate from high-turnover tissues, while low-proliferating tissues, like skeletal muscle, exhibit a lower incidence of tumor development. In Duchenne muscular dystrophy (DMD), which induces increased skeletal muscle regeneration, tumor incidence is increased. Rhabdomyosarcomas (RMSs), a rare and aggressive type of soft tissue sarcoma, can develop in this context, but the impact of DMD severity on RMS development and its cell of origin are poorly understood. Read More