S.P.2 Disease progression as measured by the 6MWD in Duchenne Muscular Dystrophy; a single centre experience of 62 boys treated with daily corticosteroids

2012 ◽  
Vol 22 (9-10) ◽  
pp. 876
Author(s):  
N.M. Goemans ◽  
M. van den Hauwe ◽  
A. van Impe ◽  
T. Mercier ◽  
R. Wilson ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Single Centre ◽  
Single Centre Experience

scholarly journals Quantitative muscle ultrasound detects disease progression in Duchenne muscular dystrophy

2017 ◽  
Vol 81 (5) ◽  
pp. 633-640 ◽  
Author(s):  
Craig M. Zaidman ◽  
Jim S. Wu ◽  
Kush Kapur ◽  
Amy Pasternak ◽  
Lavanya Madabusi ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Muscle Ultrasound

scholarly journals Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

2019 ◽  
Vol 8 ◽  
pp. 204800401987958
Author(s):  
HR Spaulding ◽  
C Ballmann ◽  
JC Quindry ◽  
MB Hudson ◽  
JT Selsby
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Mdx Mice ◽  
Dystrophin Deficiency ◽  
Muscle Wasting Disease ◽  
Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

scholarly journals Monitoring disease activity noninvasively in the mdx model of Duchenne muscular dystrophy

2018 ◽  
Vol 115 (30) ◽  
pp. 7741-7746 ◽  
Author(s):  
Antonio Filareto ◽  
Katie Maguire-Nguyen ◽  
Qiang Gan ◽  
Garazi Aldanondo ◽  
Léo Machado ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Premature Death ◽  
Response To Therapy ◽  
Luciferase Reporter ◽  
Luciferase Expression ◽  
Muscle Degeneration ◽  
Reporter Strain ◽  
Novel Treatments

Duchenne muscular dystrophy (DMD) is a rare, muscle degenerative disease resulting from the absence of the dystrophin protein. DMD is characterized by progressive loss of muscle fibers, muscle weakness, and eventually loss of ambulation and premature death. Currently, there is no cure for DMD and improved methods of disease monitoring are crucial for the development of novel treatments. In this study, we describe a new method of assessing disease progression noninvasively in the mdx model of DMD. The reporter mice, which we term the dystrophic Degeneration Reporter strains, contain an inducible CRE-responsive luciferase reporter active in mature myofibers. In these mice, muscle degeneration is reflected in changes in the level of luciferase expression, which can be monitored using noninvasive, bioluminescence imaging. We monitored the natural history and disease progression in these dystrophic report mice and found that decreases in luciferase signals directly correlated with muscle degeneration. We further demonstrated that this reporter strain, as well as a previously reported Regeneration Reporter strain, successfully reveals the effectiveness of a gene therapy treatment following systemic administration of a recombinant adeno-associated virus-6 (rAAV-6) encoding a microdystrophin construct. Our data demonstrate the value of these noninvasive imaging modalities for monitoring disease progression and response to therapy in mouse models of muscular dystrophy.

Abstract 16916: Asymptomatic Patients With Duchenne Muscular Dystrophy Have Elevated Troponin

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Aryaz Sheybani ◽  
Kim CRUM ◽  
Frank J Raucci ◽  
Larry W Markham ◽  
Jonathan H Soslow
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Troponin I ◽  
Statistical Significance ◽  
Myocardial Inflammation ◽  
Gadolinium Enhancement ◽  
Normal Ranges ◽  
Asymptomatic Patients ◽  
Future Drug

Introduction: Cardiomyopathy is the leading cause of death in Duchenne Muscular Dystrophy (DMD), but traditional heart failure biomarkers have limited utility. Cardiac Troponin I (cTnI) has been used in DMD research studies as a marker of toxicity, but little is known about cTnI levels in asymptomatic patients. The goal of this study was to longitudinally evaluate cTnI, NTproBNP, and BNP in an asymptomatic DMD cohort. We hypothesized the biomarkers would not correlate with cardiac function, but some asymptomatic patients would exhibit a cTnI leak, reflecting ongoing myocardial inflammation related to disease progression. Methods: Asymptomatic DMD patients (N=69) and controls with normal cardiac evaluations (N=18) were enrolled. In DMD subjects, biomarker levels were obtained at time of cardiac magnetic resonance imaging (CMR), which included assessment of atrial and ventricular volumes, function, and late gadolinium enhancement (LGE). Normal ranges for biomarkers were created based on control values. Spearman correlation was used for analysis. Results: There was no consistent correlation between biomarkers and disease progression by CMR (Table 1). Several DMD subjects had transiently elevated cTnI (Fig 1). Those with elevated cTnI trended towards being more likely to have LGE on baseline CMR, though this did not reach statistical significance (p= 0.08). Conclusions: CTnI, BNP, and NTproBNP do not correlate with CMR assessment of cardiomyopathy progression. There is a subset of the DMD cohort with asymptomatic cTnI leak. While this cTnI leak is of uncertain clinical significance, it is important to recognize if cTnI is used to assess for cardiac toxicity in future drug trials.

scholarly journals Treatment with l-citrulline and metformin in Duchenne muscular dystrophy: study protocol for a single-centre, randomised, placebo-controlled trial

Trials ◽  
2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Patricia Hafner ◽  
Ulrike Bonati ◽  
Daniela Rubino ◽  
Vanya Gocheva ◽  
Thomas Zumbrunn ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Study Protocol ◽  
Controlled Trial ◽  
Single Centre

Characteristics of Disease Progression and Genetic Correlation in Ambulatory Iranian Boys With Duchenne Muscular Dystrophy

2021 ◽  
Author(s):  
Gholamreza Zamani ◽  
Sareh Hosseinpour ◽  
Mahmoud Reza Ashrafi ◽  
Mahmoud Mohammadi ◽  
Reza Shervin Badv ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Motor Function ◽  
Pediatric Population ◽  
Disease Onset ◽  
Clinical History ◽  
Disease Diagnosis ◽  
The Mean ◽  
Mutation Type

Abstract Introduction: Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in the pediatric population. The manifestations are progressive muscle weakness, impairment in walking and motor function leading to loss of ambulation by age of 13 years. Molecular studies are standard tests for diagnosis. This article describes the status of disease progression and genetic pattern in the Iranian affected boys and furthermore, concerns to find a correlation between the genotype and motor function phenotype of them. Methods This study was performed on 152 DMD patients. Clinical history including disease phenotype, steroid therapy data and the NorthStar Ambulatory Assessment (NSAA) score were all collected. Molecular diagnoses were confirmed by multiplex ligation dependent probe amplification and Next Generation Sequencing tests. Results We studied a total of 152 Iranian DMD patients. The mean age at disease onset was 4.04 ± 2.00 year and the mean age at diagnosis was 5.05 ± 2.08 year. The mean age of loss of ambulatory was 10.9 year. Contracture was seen in 38.9 %. The overall mean of NSAA total score versus age of the patients peaked at 4 year with mean NSAA score of 24. We assessed the yearly changes in the NSAA linear score for all cases based on mutation type and exon site. We found deletion mutation in 79.1%, duplication in 6.8%, nonsense in 12.8%, and splice site in 1.4%. The most common single exon was deletion exon 44 in our patients (5.3%) and the most common multiexon deletion was 45–50 and 45–52 exon equally with 4.6%. This study did not show any correlation between age at disease onset, loss of ambulation age and wheelchair dependency with mutation type but a correlation between contracture with mutation type was found. A significant deference in NSAA score were seen between deletion and nonsense groups at the age of 3 year (P = 0.036) and 3.5 years (p = 0.04). We couldn’t find any correlation among phenotype and Exon site. 91.1% had a history of corticosteroid taking and 54.1% of patient had compliance with rehabilitation. Conclusion This study has demonstrated the phenotype and mutational features of DMD boys and provide information of the disease natural motor history, disease progression and disease diagnosis with the management status of DMD in Iran. Achieved data will encourage the development of clinical trials and advance future molecular therapies in Iran.

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