Therapeutic potential of miRNAs in Duchenne muscular dystrophy and other neuromuscular diseases

2020 ◽  
Author(s):  
Yuxing Xia
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Therapeutic Potential ◽  
Neuromuscular Diseases

scholarly journals Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Junio Dort ◽  
Zakaria Orfi ◽  
Paul Fabre ◽  
Thomas Molina ◽  
Talita C. Conte ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gold Standard ◽  
Therapeutic Potential ◽  
Preclinical Study ◽  
Myogenic Cells ◽  
Inflammatory Phenotype ◽  
Myogenic Factors ◽  
Myogenic Progenitor Cells

AbstractLack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by dampening the chronic and excessive inflammatory process; however, they also have numerous harmful side effects that hamper their therapeutic potential. Here, we investigated Resolvin-D2 as a new therapeutic alternative having the potential to target multiple key features contributing to the disease progression. Our in vitro findings showed that Resolvin-D2 promotes the switch of macrophages toward their anti-inflammatory phenotype and increases their secretion of pro-myogenic factors. Moreover, Resolvin-D2 directly targets myogenic cells and promotes their differentiation and the expansion of the pool of myogenic progenitor cells leading to increased myogenesis. These effects are ablated when the receptor Gpr18 is knocked-out, knocked-down, or blocked by the pharmacological antagonist O-1918. Using different mouse models of DMD, we showed that Resolvin-D2 targets both inflammation and myogenesis leading to enhanced muscle function compared to glucocorticoids. Overall, this preclinical study has identified a new therapeutic approach that is more potent than the gold-standard treatment for DMD.

Differential diagnosis of Duchenne muscular dystrophy

2021 ◽  
Vol 2 (3) ◽  
pp. 159-166
Author(s):  
Alexey L. Kurenkov ◽  
Lyudmila M. Kuzenkova ◽  
Lale A. Pak ◽  
Bella I. Bursagova ◽  
Tatyana V. Podkletnova ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Damage ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Neuromuscular Diseases ◽  
Muscular Dystrophies ◽  
Juvenile Form ◽  
Pathogenic Variants

Duchenne muscular dystrophy (DMD) is a disease with an X-linked recessive type of inheritance, belonging to a group of disorders with primary muscle damage, caused by pathogenic variants in the DMD gene and associated with dysfunction of the dystrophin protein. Since DMD is manifested by the gradual development of progressive, mainly proximal muscle weakness, the differential diagnosis is primarily carried out in the group of diseases with muscle damage - myopathies. Among these diseases, the leading candidates for differential diagnosis are hereditary myopathies (limb-girdle muscular dystrophies, facioscapulohumeral dystrophy, congenital muscular dystrophies, glycogenoses - the most common juvenile form of glycogenosis type II (Pompe disease)) and, much less often, congenital myopathies and other conditions of neuromuscular diseases). When conducting a differential diagnosis in a child with suspected DMD, the age of the onset of the disease, early initial clinical manifestations and the development of symptoms as they grow, genealogical analysis, laboratory tests (the level of creatine kinase, aspartate aminotransferase, alanine aminotransferase in blood serum), instrumental (electromyography, magnetic resonance imaging of the brain and muscles) and molecular genetics (polymerase chain reaction, multiplex ligation-dependent probe amplification, next-generation sequencing, Sanger sequencing, etc.) of studies, and in some cases, muscle biopsy data. Knowledge of the nuances of the differential diagnosis allows establishing a genetic diagnosis of DMD as early as possible, which is extremely important for the formation of the prognosis of the disease and the implementation of all available treatment methods, including pathogenetic therapy, and is also necessary for medical and genetic counselling of families with DMD patients.

scholarly journals Hunting for a cure: The therapeutic potential of gene therapy in Duchenne muscular dystrophy

2014 ◽  
Vol 26 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Hasnur Zaman Hashim ◽  
Shahrin Tarmizi Che Abdullah ◽  
Wan Aliaa Wan Sulaiman ◽  
Fan Kee Hoo ◽  
Hamidon Basri
Keyword(s):  
Gene Therapy ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Therapeutic Potential

Proteins in the Urine Associated with Duchenne Muscular Dystrophy and other Neuromuscular Diseases

1981 ◽  
Vol 61 (2) ◽  
pp. 141-149 ◽  
Author(s):  
N. Frearson ◽  
R. D. Taylor ◽  
S. V. Perry
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Physical Disabilities ◽  
Protein Pattern ◽  
Neuromuscular Diseases ◽  
Two Dimensional Electrophoresis ◽  
Characteristic Features ◽  
Neuromuscular Conditions ◽  
Dimensional Electrophoresis ◽  
Healthy Persons

1. Up to 200 protein staining spots could be detected on two-dimensional electrophoresis of urine from healthy persons. Other minor spots were occasionally present. 2. Although the electropherograms exhibited constant characteristic features some variation in protein pattern was observed between individuals and with a given individual at different times. 3. Two additional proteins, spots C and D, were consistently present in urine from boys with Duchenne muscular dystrophy. Spot C was also present in the urine of about 60% of obligatory carriers of this dystrophy. 4. The protein responsible for spot C had a molecular weight of 26000 and an isoelectric point of 5.3. 5. Spot C was also detected in the urine of patients with other neuromuscular conditions. Neither spot C nor spot D could be detected in the urine of patients with physical disabilities other than those of neuromuscular origin. 6. It is concluded that the urinary excretion of spot C, and probably of spot D, is a consequence of muscle damage and that their detection has potential as a diagnostic tool.

scholarly journals Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy

2017 ◽  
Vol 114 (23) ◽  
pp. 6080-6085 ◽  
Author(s):  
Natassia M. Vieira ◽  
Janelle M. Spinazzola ◽  
Matthew S. Alexander ◽  
Yuri B. Moreira ◽  
Genri Kawahara ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Neuromuscular Diseases ◽  
Genetic Modifiers ◽  
Cardiorespiratory Failure ◽  
Transfer Protein ◽  
Phosphorylated Akt ◽  
Phosphatidylinositol Transfer Protein ◽  
Phosphatidylinositol Transfer ◽  
Dystrophin Protein

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy. In a Brazilian golden retriever muscular dystrophy (GRMD) dog colony, two related dogs demonstrated strikingly mild dystrophic phenotypes compared with those typically observed in severely affected GRMD dogs despite lacking dystrophin. Microarray analysis of these “escaper” dogs revealed reduced expression of phosphatidylinositol transfer protein-α (PITPNA) in escaper versus severely affected GRMD dogs. Based on these findings, we decided to pursue investigation of modulation of PITPNA expression on dystrophic pathology in GRMD dogs, dystrophin-deficient sapje zebrafish, and human DMD myogenic cells. In GRMD dogs, decreased expression of Pitpna was associated with increased phosphorylated Akt (pAkt) expression and decreased PTEN levels. PITPNA knockdown by injection of morpholino oligonucleotides in sapje zebrafish also increased pAkt, rescued the abnormal muscle phenotype, and improved long-term sapje mutant survival. In DMD myotubes, PITPNA knockdown by lentiviral shRNA increased pAkt and increased myoblast fusion index. Overall, our findings suggest PIPTNA as a disease modifier that accords benefits to the abnormal signaling, morphology, and function of dystrophic skeletal muscle, and may be a target for DMD and related neuromuscular diseases.

scholarly journals First Regulatory Qualification of a Novel Digital Endpoint in Duchenne Muscular Dystrophy: A Multi-Stakeholder Perspective on the Impact for Patients and for Drug Development in Neuromuscular Diseases

2021 ◽  
pp. 183-190
Author(s):  
Laurent Servais ◽  
Eric Camino ◽  
Aude Clement ◽  
Craig M. McDonald ◽  
Jacek Lukawy ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Drug Development ◽  
Neuromuscular Diseases ◽  
European Medicines Agency ◽  
Motor Abilities ◽  
Stakeholder Perspective ◽  
Functional Outcome Measures ◽  
Multi Stakeholder ◽  
The Impact

<b><i>Background:</i></b> Functional outcome measures used to assess efficacy in clinical trials of investigational treatments for rare neuromuscular diseases like Duchenne muscular dystrophy (DMD) are performance-based tasks completed by the patient during hospital visits. These are prone to bias and may not reflect motor abilities in real-world settings. Digital tools, such as wearable devices and other remote sensors, provide the opportunity for continuous, objective, and sensitive measurements of functional ability during daily life. Maintaining ambulation is of key importance to individuals with DMD. Stride velocity 95th centile (SV95C) is the first wearable acquired digital endpoint to receive qualification from the European Medicines Agency (EMA) to quantify the ambulation ability of ambulant DMD patients aged ≥5 years in drug therapeutic studies; it is also currently under review for the US Food and Drug Administration (FDA) qualification. <b><i>Summary:</i></b> Focusing on SV95C as a key example, we describe perspectives of multiple stakeholders on the promise of novel digital endpoints in neuromuscular disease drug development.

Mesenchymal Stem Cells for Regenerative Medicine for Duchenne Muscular Dystrophy

2020 ◽  
Author(s):  
Ahmed Elhussieny ◽  
Ken’ichiro Nogami ◽  
Fusako Sakai-Takemura ◽  
Yusuke Maruyama ◽  
AbdElraouf Omar Abdelbakey ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Regenerative Medicine ◽  
Therapeutic Potential ◽  
Dystrophic Muscle ◽  
Multipotent Stem Cells ◽  
Pharmacological Target

Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from both foetal and adult tissues. Several groups demonstrated that transplantation of MSCs promoted the regeneration of skeletal muscle and ameliorated muscular dystrophy in animal models. Mesenchymal stem cells in skeletal muscle, also known as fibro-adipogenic progenitors (FAPs), are essential for the maintenance of skeletal muscle. Importantly, they contribute to fibrosis and fat accumulation in dystrophic muscle. Therefore, MSCs in muscle are a pharmacological target for the treatment of muscular dystrophies. In this chapter, we briefly update the knowledge on mesenchymal stem/progenitor cells and discuss their therapeutic potential as a regenerative medicine treatment of Duchenne muscular dystrophy.

scholarly journals The Use of Virtual Reality Technologies in the Treatment of Duchenne Muscular Dystrophy: Systematic Review (Preprint)

2020 ◽  
Author(s):  
Maria Rosa Baeza-Barragán ◽  
Maria Teresa Labajos Manzanares ◽  
Carmen Ruiz Vergara ◽  
María Jesús Casuso-Holgado ◽  
Rocío Martín-Valero
Keyword(s):  
Systematic Review ◽  
Virtual Reality ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Systematic Reviews ◽  
New Technologies ◽  
Neuromuscular Diseases ◽  
Cochrane Library ◽  
Upper Limbs ◽  
Rehabilitation Programs

BACKGROUND Duchenne muscular dystrophy is a serious and progressive disease affecting one in 3500-6000 live male births. The use of new virtual reality technologies has revolutionized the world of youth rehabilitation. OBJECTIVE We performed a systematic review to study the effectiveness of the use of virtual reality systems applied in the rehabilitation of the upper limbs of individuals with Duchenne muscular dystrophy. METHODS Between June 2018 and September 2019, we carried out a series of searches in 5 scientific databases: (1) PubMed, (2) Web of Science, (3) Scopus, (4) The Cochrane Library, and (5) MEDLINE via EBSCO. Two evaluators independently conducted the searches following the PRISMA recommendations for systematic reviews for articles. Two independent evaluators collated the results. Article quality was determined using the PEDro scale. RESULTS A total of 7 clinical trials were included in the final review. These studies used new technologies as tools for physiotherapeutic rehabilitation of the upper limbs of patients with Duchenne muscular dystrophy. Collectively, the studies showed improvement in functionality, quality of life, and motivation with the use of virtual reality technologies in the rehabilitation of upper limbs of individuals with Duchenne muscular dystrophy. CONCLUSIONS The treatment of neuromuscular diseases has changed in recent years, from palliative symptom management to preventive methods for capacity building. The use of virtual reality is beginning to be necessary in the treatment of progressive diseases involving movement difficulties, as it provides freedom and facilitates the improvement of results in capacity training. Given that new technologies are increasingly accessible, rehabilitation and physiotherapy programs can use these technologies more frequently, and virtual reality environments can be used to improve task performance, which is essential for people with disabilities. Ultimately, virtual reality can be a great tool for physiotherapy and can be used for Duchenne muscular dystrophy rehabilitation programs to improve patient performance during training. CLINICALTRIAL PROSPERO International Prospective Register of Systematic Reviews CRD42018102548; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=102548

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