Passarelli, C, Selvatici, R, Carrieri, A, Di Raimo, FR, Falzarano, MS, Fortunato, F et al.. Tumor Necrosis Factor Receptor SF10A (TNFRSF10A) SNPs Correlate With Corticosteroid Response in Duchenne Muscular Dystrophy. Front Genet. 2020.11 605 PMID:32719714. Strandberg, K, Ayoglu, B, Roos, A, Reza, M, Niks, E, Signorelli, M et al.. Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy. J Neuromuscul Dis. 2020.7 (3)231-246 PMID:32390640. Landfeldt, E, Thompson, R, Sejersen, T, McMillan, HJ, Kirschner, J, Lochmüller, H et al.. Life expectancy at birth in Duchenne muscular dystrophy: a systematic review and meta-analysis. Eur. J. Epidemiol. 2020.35 (7)643-653 PMID:32107739. Capitanio, D, Moriggi, M, Torretta, E, Barbacini, P, De Palma, S, Viganò, A et al.. Comparative proteomic analyses of Duchenne muscular dystrophy and Becker muscular dystrophy muscles: changes contributing to preserve muscle function in Becker muscular dystrophy patients. J Cachexia ...
It worsens quickly. Other muscular dystrophies (including ) get worse much more slowly.. Duchenne muscular dystrophy is caused by a defective gene for dystrophin (a protein in the muscles). However, it often occurs in people without a known family history of the condition.. The condition most often affects boys due to the way the disease is inherited. The sons of women who are carriers of the disease (women with a defective gene, but no symptoms themselves) each have a 50% chance of having the disease. The daughters each have a 50% chance of being carriers. Very rarely, a female can be affected by the disease.. Duchenne muscular dystrophy occurs in about 1 out of every 3,600 male infants. Because this is an inherited disorder, risks include a family history of Duchenne muscular dystrophy. ...
UCLAs cutting-edge Duchenne muscular dystrophy research funded by Californias stem cell agency. Stem cell gene therapy approach developed at UCLA holds promise for 60 percent of patients with the deadly disease. July 21, 2016. Scientists at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and Center for Duchenne Muscular Dystrophy at UCLA have received funding from Californias stem cell agency for the next phase of cutting-edge stem cell gene therapy research that could eventually produce a treatment for Duchenne muscular dystrophy, which affects approximately 1 in 5,000 boys in the U.S. and is the most common fatal childhood genetic disease. The grant, awarded to scientists April Pyle, Melissa Spencer and Huan Meng, totals $2,150,400. The decision to fund the research was made during todays meeting of the California Institute for Regenerative Medicines governing board.. The researchers will utilize a stem cell gene editing technology called CRISPR/Cas9 ...
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MCQS DUCHENNE MUSCULAR DYSTROPHY DUCHENNE MUSCULAR DYSTROPHY PLAB, IELTS, USMLE, GRE, AIPGMEE, AIIMS, AFMC, BHU, CMC, JIPMER, PGI, SGPGI, ...
Duchenne muscular dystrophy is a highly complex multi-system disorder caused by primary abnormalities in the Dmd gene encoding the membrane cytoskeletal protein dystrophin. The resulting loss of the dystrophin protein triggers a concomitant disintegration of the dystrophin-associated glycoprotein complex at the sarcolemma. This complex links intracellular actin to components of the extracellular matrix and serves as a stabilising support network during normal muscle excitation-contraction-relaxation cycles. In Duchenne muscular dystrophy, the loss of dystrophin and its associated protein complex leads to membrane instability and micro-rupturing, the influx of excessive levels of calcium ions, the activation of proteases, sterile inflammation and eventually muscle degeneration and infiltration of adipose and connective tissue. Affected children suffer from severe and progressive skeletal muscle wasting with a loss of independent ambulation occurring during the early teenage years. In addition to ...
Duchenne/Becker muscular dystrophy (DMD/BMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b extension trial that will evaluate the long-term safety of ataluren (PTC124) in boys with nonsense mutation DMD/BMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, and other important clinical and laboratory measures ...
Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. Antisense-mediated exon skipping is one of the most promising approaches for the treatment of DMD but still faces personalized medicine challenges as different mutations found in DMD patients require skipping of different exons. However, 70% of DMD patients harbor dystrophin gene deletions in a mutation-rich area or hot-spot in the central genomic region. In this study, we have developed 11 different U7 small-nuclear RNA, to shuttle antisense sequences designed to mask key elements involved in the splicing of exons 45 to 55. We demonstrate that these constructs induce efficient exon skipping both in vitro in DMD patients myoblasts and in vivo in human DMD (hDMD) mice and that they can be combined into a single vector to achieve a multi skipping of at least 3 exons. These very encouraging results provide proof of principle that efficient multiexon-skipping can be achieved using adeno
Koenig M, Beggs A, Moyer M, Scherpf S, Heindrich K, Bettecken T, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet. 1989;45:498-506. Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987 Jul 31;50:509-17. Kenwrick S, Patterson M, Speer A, Fischbeck K, Davies K. Molecular analysis of the Duchenne muscular dystrophy region using pulsed field gel electrophoresis. Cell. 1987 Jan 30;48:351-7. Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Gappmaier E, Howard MT, et al. Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. Hum Mutat. 2009 Dec;30:1657-66. Tuffery-Giraud S, Beroud C, Leturcq F, Yaou RB, Hamroun D, Michel-Calemard L, et al. Genotype-phenotype ...
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, leading to reduced/abnormal dystrophin. Becker muscular dystrophy (BMD) is a milder form, caused by the same mutation, with a nearly normal life expectancy, but with a 50% chance of cardiac involvement (CI) (1). Although female carriers are usually free of symptoms, they may develop peripheral myopathy and cardiomyopathy, contributing to heart failure (HF) (1).. Our aim was to evaluate the possibility of myocardial damage in genetically confirmed mothers-carriers of Duchenne muscular dystrophy (DMDc) and Becker muscular dystrophy (BMDc) using cardiac magnetic resonance (CMR).. Thirty-five mothers, mean age 50 years (range: 32 to 68 years), without known comorbidities, except mild hypertension (systolic blood pressure 160 to 170 mm Hg in 1 DMDc and 1 BMDc), were studied. DMDc (n = 25) and BMDc (n = 10) were prospectively evaluated by CMR using a 1.5-T General Electric Signa HDxt (Milwaukee, Wisconsin). A standard steady-state ...
Antisense Therapeutics Ltd. is looking to raise A$1.6 million in a share placement to fund its development of the ATL1102 drug for Duchenne muscular dystrophy.. Duchenne muscular dystrophy, or DMD, is a genetic disorder characterized by progressive muscle degeneration and weakness that could lead to death.. The company will issue 48,484,848 shares at 3 Australian cents apiece in the transaction. The placement is backed by Australian Ethical Investment and Platinum Asset Management, the companys major healthcare institutional shareholders.. Antisense Therapeutics plans to seek regulatory approval to conduct a phase 2b clinical study for ATL1102 among DMD patients in Europe.. XEC Partners is acting as lead manager in the placement.. Toorak, Victoria-based Antisense Therapeutics is engaged in the development and commercialization of antisense therapeutics to treat DMD, multiple sclerosis and acromegaly.. ...
Researchers describe how increased production of a microRNA promotes progressive muscle deterioration in a mouse model of Duchenne muscular dystrophy (DMD), according to a study published online on January 2, 2012 in the Journal of Cell Biology. As DMD patients age, their damaged muscle cells are gradually replaced by collagen-rich, fibrous tissue. This muscle fibrosis is partly induced by the growth factor TGF-beta, which is highly activated in DMD patients, though exactly how this cytokine promotes fibrogenesis is unclear. Dr. Pura Muñoz-Cánoves and colleagues examined the role of miR-21, a microRNA whose production is stimulated by TGF-beta signaling. miR-21 was upregulated in the collagen-producing fibroblasts of both DMD patients and mice that develop disease symptoms similar to human muscular dystrophy (so-called mdx mice). Inhibiting miR-21 reduced collagen levels and prevented, or even reversed, fibrogenesis in diseased mice, whereas mdx mice overexpressing the microRNA produced more ...
along with other high-profile winners, including Sharon Stone, Mariska Hargitay, and Cynthia Nixon.. About Duchenne Muscular Dystrophy (DMD):. Duchenne Muscular Dystrophy is the most common fatal genetic disorder to affect children around the world. Children with DMD cannot produce dystrophin, a protein necessary for muscle strength and function. As a result, every skeletal muscle in the body deteriorates. Although Duchenne is the most common fatal genetic disorder to affect children, there is no cure.. About Cookie Magazine. Cookie is a family lifestyle magazine published by Condé Nast Publications and the winner of Ad Ages 2007 Launch of the Year. Tailored to the sensibilities of parents with young children, it covers fashion, travel, food, health, home, and beauty in a modern way, giving moms permission to retain their "pre-motherhood" sense of style and adventure. For more information, please visit www.cookiemag.com.. # # #. ...
The cap capacity in nine Duchenne muscular dystrophy (DMD) patients and in 23 healthy male subjects (14 adults and nine neonates) has been investigated by inducing capping of HLA molecules. The evaluation of capping percentages ranged in healthy controls from 44 to 61 with a mean value of 53.39 +/- 4.89, while DMD patients displayed cap capacity of percentages varying from 15 to 38 with a mean value of 31.5 +/- 7.42. Statistical significance of the differences between the two groups, assessed by the Mann-Whitney U test, was p less than 0.00003. A correlation was found in DMD patients between cap capacity and age (tau = +0.657, p = 0.012). The results confirm previous reports of Ig capping impairment noted in B cells of the whole lymphocyte population, supporting the hypothesis of a systemic cellular defect in DMD patients. The data obtained suggest that HLA capping could overcome some of the technical difficulties of Ig capping and could be used as a diagnostic aid in antenatal detection of ...
Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressive muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene. Play media Some symptoms consistent with Becker muscular dystrophy are: Muscle weakness, slowly progressive difficulty walking Severe upper extremity muscle weakness. Toe-walking Use of Gowers Maneuver to get up from floor. Difficulty breathing Skeletal deformities, chest and back (scoliosis) Pseudohypertrophy of calf muscles Muscle cramps Heart muscle problems Elevated Creatine kinase levels in blood Individuals with this disorder typically experience progressive muscle weakness of the leg and pelvis muscles, which is associated with a loss of muscle mass (wasting). Muscle weakness also occurs in the ...
TY - JOUR. T1 - Profiles of neuromuscular diseases. Duchenne muscular dystrophy.. AU - McDonald, Craig M. AU - Abresch, R. T.. AU - Carter, G. T.. AU - Fowler, W. M.. AU - Johnson, E. R.. AU - Kilmer, D. D.. AU - Sigford, B. J.. PY - 1995/9. Y1 - 1995/9. N2 - One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were followed over a 10-yr period to provide a profile of impairment and disability. The median height and weight of DMD boys were normally distributed before ages 9-10, but during the second decade height was markedly reduced, and weight was no longer normally distributed. Younger boys gained more weight than normals, whereas older individuals actually showed weight loss. Manual muscle test (MMT) measurements showed loss of strength in a fairly linear fashion from ages 5-13 yr, -0.25 MMT units per year. Upper extremity muscles were stronger than lower extremity muscles, proximal muscle groups were weaker than distal muscle groups, and extensor muscles were weaker ...
Dystrophinopathy is a term of X-linked recessive genetic disease, including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, and the X-linked dilated cardiomyopathy. The aim of this study is to determine the clinical spectrum and natural progression of dystrophinopathy in a prospective multicenter natural history study, to assess the clinical, genetic of patients with dystrophinopathy to optimize clinical management ...
A new study from UT Southwestern suggests that more people with Duchenne muscular dystrophy could live longer by identifying and more aggressively treating patients with certain risk factors.
TY - JOUR. T1 - Hip kinetics during gait are clinically meaningful outcomes in young boys with Duchenne muscular dystrophy. AU - Heberer, Kent. AU - Fowler, Eileen. AU - Staudt, Loretta. AU - Sienko, Susan. AU - Buckon, Cathleen E.. AU - Bagley, Anita. AU - Sison-Williamson, Mitell. AU - McDonald, Craig M. AU - Sussman, Michael D.. PY - 2016/7/1. Y1 - 2016/7/1. N2 - Duchenne muscular dystrophy (DMD) is an X-linked genetic neuromuscular disorder characterized by progressive proximal to distal muscle weakness. The success of randomized clinical trials for novel therapeutics depends on outcome measurements that are sensitive to change. As the development of motor skills may lead to functional improvements in young boys with DMD, their inclusion may potentially confound clinical trials. Three-dimensional gait analysis is an under-utilized approach that can quantify joint moments and powers, which reflect functional muscle strength. In this study, gait kinetics, kinematics, spatial-temporal ...
...Duchenne muscular dystrophy research at the University of Florida got ...UF scientists will assess whether MRI technology can be used as a prec...Duchenne muscular dystrophy affects about one of every 3500 to 5000 ... The lack of a reliable assessment tool for measuring muscle function ...,NIH,awards,$7.5,million,to,study,MRI,as,a,tool,to,evaluate,children,with,muscular,dystrophy,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
A new study from the University of Liverpool, has identified high amounts of a neutrophil-derived protein in the muscle of a Duchenne muscular dystrophy (DMD) mouse model. The finding shows that the protein hinders stem cells from repairing damaged muscle and it reveals a potential drug target for DMD therapies.. The study, "Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation," was published in Scientific Reports. DMD, the most common form of muscular dystrophy, is a genetic disorder caused by mutations in the dystrophin gene that lead to muscle weakness and progressive muscle loss. Dystrophin is a key component of a complex that anchors muscle fibers to the extracellular matrix. Lack of dystrophin leads to the loss of the anchorage causing muscle fibers to become sensitive to mechanical stress and damaged during contraction.. In healthy muscle, stem cells activate in response to muscle injury to rapidly proliferate ...
Mononuclear cells infiltrate degenerating muscles of Duchenne muscular dystrophy (DMD) patients. Using a quantitative PCR, we first characterized the T cells infiltrating muscle biopsies from six DMD patients. High levels of TCR V beta 2 transcripts were observed in DMD muscle tissue. TCR V beta 2 transcripts from seven DMD patients and five controls were sequenced, and the VDJ junctional region analyzed in 166 clones. One specific amino acid motif, RVSG, was found in the third complementary determining region (CDR3) of TCR V beta 2 chains in samples from five DMD patients, but not in controls. A specific immune reaction at the site of tissue degeneration may play an important role in the pathogenesis of DMD. ...
Clinical trial for Duchenne Muscular Dystrophy | Cardiomyopathies , The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
In Duchenne muscular dystrophy (DMD), a disease with a prevalence of 1 in 3500 boys, an X-linked mutation of the dystrophin gene causes absence of the dystrophin protein in the muscle cell membrane. This leads to progressive loss of muscular tissue resulting in weakness and ultimately failure of skeletal, respiratory and heart musculature. The expected lifespan of DMD boys is about 27 years. In addition, about 30% of DMD patients show cognitive impairment with an unknown etiology and prognosis. Recently, the Leiden Duchenne research group showed the first successful restoration of dystrophin expression in skeletal muscle in humans. For the further development of therapies, two advances are imperative:. ...
Muscular dystrophy (MD) is a group of diseases that result in progressive muscle weakness. Duchenne muscular dystrophy (DMD) is an X-linked recessive form of MD that results from the absence of the protein dystrophin. As a result, muscle fibre membranes are damaged upon contraction to the extent that the natural regenerative properties of muscle, normally provided by primary myoblasts, are exhausted. The objective of this study was to investigate the possible role that primary myoblasts play in muscle inflammation that is observed in DMD patients. Primary myoblasts were isolated from the new murine model of DMD, D2.B10-Dmdmdx (DBA/mdx), and a purification procedure was standardized based on the adherence properties of primary myoblasts. Cultures were treated with five inflammatory stimulating treatments: lipopolysaccharide (LPS), single-stranded RNA (ssRNA), Toll-like receptor (TLR)-7 agonist, TLR-8 agonist and TLR-9 agonist. Cultures were also treated with a commercially available inflammatory ...
Antisense oligonucleotide (AO)-mediated exon skipping is a promising new therapy for Duchenne muscular dystrophy (DMD), recently demonstrating proof of principle for restoring the absent dystrophin protein in DMD patients. However, the range of AO chemistries available for exon skipping is limited; effective systemic dystrophin protein restoration has yet to be demonstrated and will be required for disease modification in patients; and the current approach is mutation-specific, necessitating the development of multiple AO drugs to treat all DMD patients. This is therefore a highly complex drug development challenge.
Duchenne muscular dystrophy (DMD) (OMIM #310200) is an X-linked recessive inherited muscle-wasting disease characterised primarily by progressive weakness and atrophy of the skeletal and cardiac muscle. DMD patients are typically wheelchair-bound by 12 years of age and die in their late teens or early twenties of respiratory failure. It is one of the most common Mendelian disorders, occurring in all population groups with a birth prevalence of approximately 1/3 500 males. The disease gene, DMD, linked to chromosome Xp21.2, was one of the first genes to be isolated by positional cloning,[1] and the deficient product in affected boys was then identified as the protein dystrophin.[2] Dystrophin localises to the cell membrane in muscle cells and binds the protein actin, in this way forming part of the protein complex which links the cytoskeleton with the cell membrane. The gene is extremely large, spanning 2 400 kb of genomic DNA and comprising 79 exons which encode a 14 kb transcript. Causative ...
Carrie Miceli, Ph.D.. Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder primarily caused by large frameshifting deletions in the DMD gene that result in a loss of dystrophin protein expression. Antisense oligonucleotide (AO)-mediated exon skipping shows promise as a therapeutic approach by restoring the DMD reading frame, allowing internally deleted but partially functional dystrophin production and restoration of the dystrophin associated glycoprotein complex. We identified Dantrolene, an FDA approved drug, as an enhancer of exon skipping when administered with AO. We aim to establish optimal Dantrolene formulation, delivery route, Dantrolene/AO dose, and test efficacy of long term treatment of optimal Dantrolene/AO on exon skipping and muscle function in vivo, establish efficacy and dosing of combinatorial therapy in multiple exon 51-skippable patient-derived fibroblasts differentiated into myotubes, and establish a DMD xenograft model system for studying DMD in ...
We appreciated the interest of Drs Giglio and Mangiola in our muscular dystrophy (MD) case report.1 We agree with the suggestion of White et al2 that for clinical diagnosis, duplications in the dystrophin gene should be treated with special care. Indeed, multiplex ligation-dependent probe amplification was performed in both the child with Duchenne muscular dystrophy (DMD) and his mother, proving the diagnosis. We also mentioned in our article that serum creatine kinase levels were elevated in the DMD carrier mother. However, we do not agree with Drs Giglio and Mangiolas opinion that "skewed X-chromosome inactivation assay must be performed because this factor is currently believed to be a main contributor to phenotypic manifestations in a Duchenne carrier." We do not consider the work of Yoshioka et al3 to be compelling evidence because this study was based on only 9 MD carriers. In contrast, another study comprising 107 MD carriers clearly suggested that a highly skewed X-chromosome pattern in ...
To identify serum biomarkers that allow monitoring of disease progression and treatment effects in Duchenne muscular dystrophy (DMD) patients, levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and osteopontin (OPN) were determined in 63 DMD patients on c …
Duchenne muscular dystrophy is a rare genetic disorder where the muscle growth degenerates and becomes weak. It is also one of the main types of muscular dystrophy. It is caused because of the lack of a protein called dystrophin that is essential for keeping the muscles together. The signs of this disorder start showing up in the early childhood especially between the age of 3 to 5 and mainly affecting boys and in rare cases, affecting girls as well.. This muscular disorder is not specific to any age, race or culture, however what makes it different from other muscular dystrophies is that it mostly occurs in young boys and men making it a gender specific disorder. It affects one in 3500 males with almost 20,000 cases every year, especially at birth. It happens mostly with males because they have X and Y chromosome both unlike girls who only have two X chromosomes making young men more prone to inheriting damaged genes or related disorders as they lack another X-chromosome that could make up for ...
Professor of Molecular Medicine, Darek Gorecki, and his team in the School of Pharmacy and Biomedical Sciences, are working to find a treatment that will delay the onset and slow down the progression of muscle degeneration in people with Duchenne muscular dystrophy, the most common and severe of all muscular dystrophies.. The condition is caused by a lack of dystrophin, a protein which acts like scaffolding and an anchor in muscle cells and without which these cells become damaged and then progressively lost, resulting in death of young adults. There are also brain forms of dystrophin that, when mutated, are responsible for the severe cognitive problems sometimes also seen in this condition.. There is no cure for this disease and treatments are urgently needed.. Working with mice, the research team has already identified a molecule present in dystrophic muscle cells (called P2X7) that contributes to muscle damage. By manipulating this molecule, the scientists have been able to relieve disease ...
Evidence-based recommendations on ataluren (Translarna) for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene..
Duchenne muscular dystrophy (DMD) is a deadly X-linked disease affecting 1 in 3,500 males. DMD patients suffer significant disability due to muscle issues, including to their heart muscle. Current guidelines advocate initiating early heart protective treatment, yet this treatment paradigm has not improved survival much beyond the third decade of life. Potentially promising approaches like gene therapy will take considerable time to improve outcomes.. This research group has recently shown in a DMD mouse model that certain existing drugs typically reserved for advanced heart failure patients can preserve cardiac muscle function at 80% of normal and near-completely prevents fibrosis development. This research group plans to execute a randomized, controlled clinical trial of one of these drugs plus the current standard of care vs. the current standard of care alone in patients with DMD. The treatment group is expected to show significant delays in heart disease using highly reproducible imaging ...
Abstract Duchenne muscular dystrophy DMD , caused by nonsense or frame-shift mutations in the dystrophin gene, is a progressive degenerative disease involving
Duchenne muscular dystrophy (DMD) is a progressive muscle disorder that causes the loss of both muscle function and independence. DMD is perhaps the most prevalent of the muscular dystrophies and is the most common lethal genetic disorder diagnosed during childhood today. Each year, approximately 20,000 children worldwide are born with DMD (one of every 3,500 male children ...
BACKGROUND: The aim of this study was to perform a longitudinal assessment using Quantitative Muscle Testing (QMT) in a cohort of ambulant boys affected by Duchenne muscular dystrophy (DMD) and to correlate the results of QMT with functional measures. This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT). METHODS: This is a single centre, prospective, non-randomised, study assessing QMT using the Kin Com(®) 125 machine in a study cohort of 28 ambulant DMD boys, aged 5 to 12 years. This cohort was assessed longitudinally over a 12 months period of time with 3 monthly assessments for QMT and with assessment of functional abilities, using the NSAA and the 6MWT at baseline and at 12 months only. QMT was also used in a control group of 13 healthy age-matched boys examined at baseline and at 12 months. RESULTS: There was an increase in QMT over ...
Duchenne Muscular Dystrophy is an X-linked recessive disorder. Being an X-linked disorder, DMD typically appears in males. It is caused by a defective gene for Dystrophin, which is a vital protein in muscles and is the most common and most severe form of muscular dystrophy. This disorder causes muscles to weaken over ten to twenty years, though it rapidly gets worse. All lower body muscles have the possiblity to be effected. In some cases breathing can also become effected. ...
TY - JOUR. T1 - Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. AU - Malik, Vinod. AU - Rodino-Klapac, Louise R.. AU - Viollet, Laurence. AU - Wall, Cheryl. AU - King, Wendy. AU - Al-Dahhak, Roula. AU - Lewis, Sarah. AU - Shilling, Christopher J.. AU - Kota, Janaiah. AU - Serrano-Munuera, Carmen. AU - Hayes, John. AU - Mahan, John D.. AU - Campbell, Katherine J.. AU - Banwell, Brenda. AU - Dasouki, Majed. AU - Watts, Victoria. AU - Sivakumar, Kumaraswamy. AU - Bien-Willner, Ricardo. AU - Flanigan, Kevin M.. AU - Sahenk, Zarife. AU - Barohn, Richard J.. AU - Walker, Christopher M.. AU - Mendell, Jerry R.. PY - 2010/6. Y1 - 2010/6. N2 - Objective: The objective of this study was to establish the feasibility of long-term gentamicin dosing to achieve stop codon readthrough and produce full-length dystrophin. Mutation suppression of stop codons, successfully achieved in the mdx mouse using gentamicin, represents an important evolving treatment strategy in Duchenne ...
There is currently an urgent need for biomarkers that can be used to monitor the efficacy of experimental therapies for Duchenne Muscular Dystrophy (DMD) in clinical trials. Identification of novel protein biomarkers has been limited due to the massive complexity of the serum proteome and the presence of a small number of very highly abundant proteins. Here we have utilised an aptamer-based proteomics approach to profile 1,129 proteins in the serum of wild-type and mdx (dystrophin deficient) mice. The serum levels of 96 proteins were found to be significantly altered (P | 0.001, q | 0.01) in mdx mice. Additionally, systemic treatment with a peptide-antisense oligonucleotide conjugate designed to induce Dmd exon skipping and recover dystrophin protein expression caused many of the differentially abundant serum proteins to be restored towards wild-type levels. Results for five leading candidate protein biomarkers (Pgam1, Tnni3, Camk2b, Cycs and Adamts5) were validated by ELISA in the mouse samples.
DURHAM - On Saturday, September 29, Coach Sean McDonnell, his staff, and the UNH Wildcats joined over 10,200 other coaches in the country to participate in Coach to Cure (www.coachtocuremd.org), a partnership between the American Football Coaches Association and Parent Project Muscular Dystrophy, to raise funds and awareness of Duchenne Muscular Dystrophy, the most common fatal genetic disorder of children. On Saturday, coaches from all over America wore armbands to encourage others to
DURHAM - On Saturday, September 29, Coach Sean McDonnell, his staff, and the UNH Wildcats joined over 10,200 other coaches in the country to participate in Coach to Cure (www.coachtocuremd.org), a partnership between the American Football Coaches Association and Parent Project Muscular Dystrophy, to raise funds and awareness of Duchenne Muscular Dystrophy, the most common fatal genetic disorder of children. On Saturday, coaches from all over America wore armbands to encourage others to
Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense...
Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there
Duchenne muscular dystrophy (DMD) is a fatal disease characterized by progressive skeletal muscle degeneration. Inhibition of the transcription factor nuclear factor-κ B (NF-κB), and more specifically the p65 subunit, significantly improves the phenotype of mdx mice, a murine DMD model. However, the ubiquity of NF-κB stands as an obstacle to clinical translation. In this dissertation, we explore the roles of NF-κB/p65 in the regenerative capacity of muscle-derived stem cells (MDSCs) with the goal of identifying alternative approaches to DMD treatment. We found that both cell proliferation and myogenic potential were increased in MDSCs lacking one allele of p65 (p65+/-). In wild type MDSCs, in vitro pharmacologic inhibition of the upstream activating kinase, IKKβ, increased myotube formation in a dose-dependent manner. When transplanted into mdx hind limb muscle, p65+/- MDSCs resulted in significantly larger engraftments. Furthermore, engraftments in cardiotoxin (CTX) injured muscle were ...
Fibrosis is the aberrant deposition of extracellular matrix (ECM) components during tissue healing leading to loss of its architecture and function. Fibrotic diseases are often associated with chronic pathologies and occur in a large variety of vital organs and tissues, including skeletal muscle. In human muscle, fibrosis is most readily associated with the severe muscle wasting disorder Duchenne muscular dystrophy (DMD), caused by loss of dystrophin gene function. In DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells and the functions of the muscle stem cells (satellite cells) become impeded and fibrogenic cells hyperproliferate and are overactivated, leading to the substitution of skeletal muscle with nonfunctional fibrotic tissue. Here, we review new developments in our understanding of the mechanisms leading to fibrosis in DMD and several recent advances towards reverting it, as potential treatments to attenuate disease progression ...
Duchenne Muscular Dystrophy is a disorder that affects every muscle in the body. It is a recessive genetic mutation that occurs on the X chromosome.
The Collaborative Trajectory Analysis Project (cTAP), a public-private partnership to accelerate data science solutions to critical problems in drug development for Duchenne Muscular Dystrophy (Duchenne), today announced the publication of two research studies with important implications for the design of effective clinical trials.
Duchenne muscular dystrophy is a disease that affects mostly boys, causes progressive muscle weakness and gradually steals boys ability to walk.