scholarly journals AYURVEDIC MANAGEMENT OF DUCHENNE MUSCULAR DYSTROPHY: A SHORT REVIEW

2019 ◽  
Vol 7 (1) ◽  
pp. 179-183
Author(s):  
Akshay A Patankar ◽  
Renu B Rathi
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Social Contact ◽  
Signs And Symptoms ◽  
Short Review ◽  
Receptive Language ◽  
Modern Medicine ◽  
Autism Spectrum ◽  
Neuromuscular Disorder ◽  
Significant Treatment

Duchenne muscular dystrophy is a neuromuscular disorder characterized by deficient dystrophin protein in the muscle. The main symptoms the patient presented were delay in expressive and receptive language development, visual discontent, hyperkinetic behaviour, and inability to initiate and maintain social contact with peers. The data obtained from the family, following clinical examination, laboratory investigation results and assessment of mental status were significant for the diagnosis of Autism Spectrum Disorder, hyperkinetic behaviour and Duchenne Muscular Dystrophy. In Ayurveda it has been classified under Medomamsa dusti further vitiates the Vata doshas occurs due to the Bheejabagahaavyava Dusti. In modern medicine there is no significant treatment available for this diseases while in Ayurvedic panchakrma therapy shows significant results in all signs and symptoms of this diseases.

scholarly journals Recent advances in the management of Duchenne muscular dystrophy

2015 ◽  
Vol 100 (12) ◽  
pp. 1173-1177 ◽  
Author(s):  
Eugen-Matthias Strehle ◽  
Volker Straub
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Support Groups ◽  
Clinical Care ◽  
Personalised Medicine ◽  
Molecular Genetic ◽  
Short Review ◽  
Neuromuscular Disorder ◽  
Average Life Expectancy ◽  
Term Care

Duchenne muscular dystrophy (DMD) is the commonest inherited neuromuscular disorder of childhood and mainly affects males. Over the course of the last century, the average life expectancy of these patients has doubled and now stands at ∼25 years. This progress has been made possible through advances in the diagnosis, treatment and long-term care of patients with DMD. Basic and clinical research, national and international scientific networks, and parent and patient support groups have all contributed to achieving this goal. The advent of molecular genetic therapies and personalised medicine has opened up new avenues and raised hopes that one day a cure for this debilitating orphan disease will be found. The main purpose of this short review is to enable paediatricians to have informed discussions with parents of boys with DMD about recent scientific advances affecting their child's clinical care.

scholarly journals CRISPR-Generated Animal Models of Duchenne Muscular Dystrophy

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 342 ◽  
Author(s):  
Kenji Rowel Q. Lim ◽  
Quynh Nguyen ◽  
Kasia Dzierlega ◽  
Yiqing Huang ◽  
Toshifumi Yokota
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Animal Models ◽  
Mechanical Stress ◽  
Muscle Cell ◽  
Neuromuscular Disorder ◽  
Reading Frame ◽  
Advantages And Disadvantages ◽  
Short Palindromic Repeat ◽  
Dmd Gene

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disorder most commonly caused by mutations disrupting the reading frame of the dystrophin (DMD) gene. DMD codes for dystrophin, which is critical for maintaining the integrity of muscle cell membranes. Without dystrophin, muscle cells receive heightened mechanical stress, becoming more susceptible to damage. An active body of research continues to explore therapeutic treatments for DMD as well as to further our understanding of the disease. These efforts rely on having reliable animal models that accurately recapitulate disease presentation in humans. While current animal models of DMD have served this purpose well to some extent, each has its own limitations. To help overcome this, clustered regularly interspaced short palindromic repeat (CRISPR)-based technology has been extremely useful in creating novel animal models for DMD. This review focuses on animal models developed for DMD that have been created using CRISPR, their advantages and disadvantages as well as their applications in the DMD field.

scholarly journals Case Report: The Genetic Diagnosis of Duchenne Muscular Dystrophy in the Middle East

2021 ◽  
Vol 9 ◽  
Author(s):  
Fouad Alghamdi ◽  
Asmaa Al-Tawari ◽  
Hadil Alrohaif ◽  
Walaa Alshuaibi ◽  
Hicham Mansour ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Management ◽  
Best Practice ◽  
Middle Eastern ◽  
Genetic Diagnosis ◽  
Signs And Symptoms ◽  
Best Practice Guidelines ◽  
Related Quality

The timely and accurate genetic diagnosis of Duchenne muscular dystrophy (DMD) enables prompt initiation of disease management and genetic counseling and optimal patient care. Despite the existence of best practice guidelines for the diagnosis of DMD, implementation of these recommendations in different parts of the world is challenging. Here, we present 4 unique case studies which illustrate the different diagnostic pathways of patients with DMD in Middle Eastern countries and highlight region-specific challenges to achieving timely and accurate genetic diagnosis of DMD. A lack of disease awareness and consequential failure to recognize the signs and symptoms of DMD significantly contributed to the delayed diagnoses of these patients. Additional challenges included limited available funding for genetic testing and a lack of local specialist and genetic testing centers, causing patients and their families to travel vast distances for appointments in some countries. Earlier and more accurate genetic diagnosis of DMD in this region would allow patients to benefit from effective disease management, leading to improvements in health-related quality of life.

scholarly journals Descriptive Characteristics of Males with Duchenne Muscular Dystrophy in Those Covered by Government (Medicaid) and Non-government (Private) Health Plans

US Neurology ◽  
2018 ◽  
Vol 14 (2) ◽  
pp. 88
Author(s):  
Oscar Henry Mayer ◽  
John Karafilidis ◽  
Kate Higgins ◽  
Brian Griffin ◽  
◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Clinical Characteristics ◽  
International Classification Of Diseases ◽  
Neuromuscular Disorder ◽  
Healthcare Resource Utilization ◽  
Office Visits ◽  
Mechanical Ventilators ◽  
Classification Of Diseases ◽  
Male Patients

Duchenne muscular dystrophy (DMD) is a rare, inherited neuromuscular disorder.Methods:To describe the clinical characteristics and healthcare resource utilization (HCRU) of male patients with DMD in commercial and Medicaid cohorts, this retrospective study identified male patients in the Truven Health MarketScan® Commercial and Medicaid databases diagnosed with hereditary progressive muscular dystrophy (HPMD) presumed to have DMD between 2011–2014. Patients with ≥2 medical claims with a diagnosis for HPMD (International Classification of Diseases, 9th revision, ClinicalModification:359.1) were included. Patients were followed for 12 months after diagnosis date, during which clinical characteristics and HCRU were assessed.Results:In total, 2,285 patients met the selection criteria. In these patients, corticosteroid and anti-infective agents were commonly utilized. Physician office visits were extremely common, with over 70% of all patients having at least one visit. Wheelchairs were commonly used, with the incidence of use increasing with age. Mechanical ventilators and airway clearance devices were underrepresented in the data.Conclusion:Patients with DMD had higher annual HCRU costs when compared with a non-DMD age-matched cohort, with patients in commercial cohorts having a higher annual average cost than those in Medicaid cohorts.

Abstract 16974: Augmentation of Vasoactive Intestinal Peptide Signaling Prevents the Development of Duchenne Muscular Dystrophy-Associated Cardiomyopathy Through Inhibition of NF-κB Signaling

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jian Huang ◽  
Terry Gemelli ◽  
Xuan Jiang ◽  
Yunbeen Bae ◽  
Tara Tassin ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Cardiac Function ◽  
Vasoactive Intestinal Peptide ◽  
Biological Effects ◽  
Neuromuscular Disorder ◽  
Heart Weight ◽  
Cardiac Tissues ◽  
Isolated Cardiac Myocytes ◽  
G Protein Coupled

Duchenne muscular dystrophy (DMD) is a recessive X-linked neuromuscular disorder characterized by progressive muscle degeneration with DMD-associated cardiomyopathy being the primary mode of death. Vasoactive intestinal peptide (VIP) is a 28 amino acid neuropeptide with biological effects mediated by G protein-coupled receptors. Utilizing a genetically modified form of VIP (PB1046) targeting cardiomyocytes, we hypothesized that augmentation of VIP signaling prevents the development of DMD-associated cardiomyopathy through inhibition of NF-κB. Either PB1046 (1.5 mg/kg) or a Placebo (saline) was injected subcutaneously every other day in three mouse models: DMD mdx:Utr+/- , DMD mdx , and wild type mice starting at 4 weeks of age for a total of 8 weeks. Cardiac function was assessed by weekly echocardiography. The cardiac tissues were collected at 14 weeks of age for histological and molecular analyses. Drug-treated DMD mdx:Utr+/- mice showed preservation of cardiac function (fractional shortening 61%±0.4 vs 45%±1.3, p <0.01; n=8-12) and a marked reduction in myocardial fibrosis (2.92%±0.13 vs 6.42% ±0.39, p <0.01; n=3) compared with controls. Hydroxyproline levels within drug-treated DMD mdx:Utr+/- mice was decreased compared with controls (44.6±5.3 vs 64.3±6.9 nmol/100mg heart weight, p <0.05, n=6). RNA-Seq data revealed an upregulation of cAMP signaling with downregulation of NF-kB signaling in isolated cardiac myocytes from drug-treated DMD mdx:Utr+/- mice as compared to controls (n=3). Western blot analyses revealed increased phosphorylation of CREB (1.97±0.02 vs 1.00±0.06, p <0.05, n=5-9) with decreased phosphorylation of p65 in drug-treated DMD cardiac nuclei as compared to controls (0.62±0.06 vs 1.00±0.09, p <0.05, n=3). Collectively, the data revealed augmentation of VIP signaling prevents the development of DMD-associated cardiomyopathy in DMD mdx:Utr+/- mice. The molecular mechanism underlying the benefits of VIP signaling suggests an upregulation of cAMP-CREB signaling with downregulation of NF-kB signaling leading to inhibition of inflammation and fibrosis within drug-treated DMD hearts. VIP signaling in DMD may serve as a new therapeutic target for the treatment of DMD-associated cardiomyopathy.

scholarly journals Longitudinal metabolomic analysis of plasma enables modeling disease progression in Duchenne muscular dystrophy mouse models

2020 ◽  
Vol 29 (5) ◽  
pp. 745-755 ◽  
Author(s):  
Roula Tsonaka ◽  
Mirko Signorelli ◽  
Ekrem Sabir ◽  
Alexandre Seyer ◽  
Kristina Hettne ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Models ◽  
Neuromuscular Disorder ◽  
Mdx Mice ◽  
Cross Sectional ◽  
New Associations ◽  
Metabolomic Data ◽  
Oxide Synthase

Abstract Duchenne muscular dystrophy is a severe pediatric neuromuscular disorder caused by the lack of dystrophin. Identification of biomarkers is needed to support and accelerate drug development. Alterations of metabolites levels in muscle and plasma have been reported in pre-clinical and clinical cross-sectional comparisons. We present here a 7-month longitudinal study comparing plasma metabolomic data in wild-type and mdx mice. A mass spectrometry approach was used to study metabolites in up to five time points per mouse at 6, 12, 18, 24 and 30 weeks of age, providing an unprecedented in depth view of disease trajectories. A total of 106 metabolites were studied. We report a signature of 31 metabolites able to discriminate between healthy and disease at various stages of the disease, covering the acute phase of muscle degeneration and regeneration up to the deteriorating phase. We show how metabolites related to energy production and chachexia (e.g. glutamine) are affected in mdx mice plasma over time. We further show how the signature is connected to molecular targets of nutraceuticals and pharmaceutical compounds currently in development as well as to the nitric oxide synthase pathway (e.g. arginine and citrulline). Finally, we evaluate the signature in a second longitudinal study in three independent mouse models carrying 0, 1 or 2 functional copies of the dystrophin paralog utrophin. In conclusion, we report an in-depth metabolomic signature covering previously identified associations and new associations, which enables drug developers to peripherally assess the effect of drugs on the metabolic status of dystrophic mice.

scholarly journals miRNome profiling in Duchenne Muscular Dystrophy; Identification of Asymptomatic and Manifesting Female Carriers

2021 ◽  
Author(s):  
Nahla O Mousa ◽  
Ahmed A Sayed ◽  
Nagia Fahmy ◽  
Mariam G Elzayat ◽  
Usama Bakry ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Family Members ◽  
Neurological Complications ◽  
Neuromuscular Disorder ◽  
Muscular Weakness ◽  
Mirna Species ◽  
Dmd Gene ◽  
Circulating Levels ◽  
Female Carriers

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder that occurs due to inactivating mutations in DMD gene, leading to muscular dystrophy. Prediction of pathological complications of DMD and the identification of female carriers are important research points that aim to reduce disease burden. Herein, we describe a case of a late DMD patient and his immediate female family members, who all carry same DMD mutation and exhibited varied degrees of symptoms. In our study, we sequenced the whole miRNome in leukocytes and plasma of the family members and results were validated using Real-Time PCR. Our results highlighted the role of miR-409-3p, miR-424-5p, miR-144-3p as microRNAs that show correlation with the extent of severity of muscular weakness and can be used for detection of asymptomatic carriers. Cellular and circulating levels of miR-494-3p had showed significant increase in symptomatic carriers, which may indicate significant roles played by this miRNA in the onset of muscular weakness. Interestingly, circulating levels of miR-206 and miR-410-3p were significantly increased only in the severely symptomatic carrier. In conclusion, our study highlighted several miRNA species, which could be used in predicting the onset of muscle and/or neurological complications in DMD carriers.

scholarly journals A novel drug-combination screen in zebrafish identifies epigenetic small molecule candidates for Duchenne muscular dystrophy

2020 ◽  
Author(s):  
Gist H. Farr ◽  
Melanie Morris ◽  
Arianna Gomez ◽  
Thao Pham ◽  
Elizabeth U. Parker ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Small Molecules ◽  
Small Molecule ◽  
Histone Deacetylase Inhibitors ◽  
Neuromuscular Disorder ◽  
Small Molecule Screen ◽  
Chemical Screen ◽  
Novel Drug

SummaryDuchenne muscular dystrophy (DMD) is a severe neuromuscular disorder and is one of the most common muscular dystrophies. There are currently few effective therapies to treat the disease, although many small-molecule approaches are being pursued. Specific histone deacetylase inhibitors (HDACi) can ameliorate DMD phenotypes in mouse and zebrafish animal models and have also shown promise for DMD in clinical trials. However, beyond these HDACi, other classes of epigenetic small molecules have not been broadly and systematically studied for their benefits for DMD. Here, we performed a novel chemical screen of a library of epigenetic compounds using the zebrafish dmd model. We identified candidate pools of epigenetic compounds that improve skeletal muscle structure in dmd zebrafish. We then identified a specific combination of two drugs, oxamflatin and salermide, that significantly rescued dmd zebrafish skeletal muscle degeneration. Furthermore, we validated the effects of oxamflatin and salermide in an independent laboratory. Our results provide novel, effective methods for performing a combination small-molecule screen in zebrafish. Our results also add to the growing evidence that epigenetic small molecules may be promising candidates for treating DMD.

scholarly journals Current Pharmacological Strategies for Duchenne Muscular Dystrophy

2021 ◽  
Vol 9 ◽  
Author(s):  
Shanshan Yao ◽  
Zihao Chen ◽  
Yuanyuan Yu ◽  
Ning Zhang ◽  
Hewen Jiang ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Symptom Relief ◽  
Standard Of Care ◽  
Neuromuscular Disorder ◽  
Therapeutic Strategies ◽  
Gene Profiling ◽  
Dystrophin Protein

Duchenne muscular dystrophy (DMD) is a lethal, X-linked neuromuscular disorder caused by the absence of dystrophin protein, which is essential for muscle fiber integrity. Loss of dystrophin protein leads to recurrent myofiber damage, chronic inflammation, progressive fibrosis, and dysfunction of muscle stem cells. There is still no cure for DMD so far and the standard of care is principally limited to symptom relief through glucocorticoids treatments. Current therapeutic strategies could be divided into two lines. Dystrophin-targeted therapeutic strategies that aim at restoring the expression and/or function of dystrophin, including gene-based, cell-based and protein replacement therapies. The other line of therapeutic strategies aims to improve muscle function and quality by targeting the downstream pathological changes, including inflammation, fibrosis, and muscle atrophy. This review introduces the important developments in these two lines of strategies, especially those that have entered the clinical phase and/or have great potential for clinical translation. The rationale and efficacy of each agent in pre-clinical or clinical studies are presented. Furthermore, a meta-analysis of gene profiling in DMD patients has been performed to understand the molecular mechanisms of DMD.

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