Reply to the letter to the editor "Gene therapy advancements in Duchenne muscular dystrophy: Overlooked challenges".

What Can We Learn From Clinical Trials of Exon Skipping for DMD?

Holter electrocardiogram should be systematic in Duchenne muscular dystrophy

Efficacy of Multi-exon Skipping Treatment in Duchenne Muscular Dystrophy Dog Model Neonates

Gene therapy in the treatment of disease

Behavior patterns in Duchenne muscular dystrophy: Report on the Parent Project Muscular Dystrophy behavior workshop 8–9 of December 2006, Philadelphia, USA

Murine models of Duchenne muscular dystrophy: is there a best model?

Although muscular dystrophy (MD) affects primarily striated muscles, smooth muscle cells of the gastrointestinal tract may also be involved. We recorded gastric electrical activity and gastric emptying time (GET) in children with MD at initial presentation and at 3-yr follow-up in order to detect gastric motor abnormalities and study their evolution along the clinical course. Twenty children with MD (median age: 4.6 yr; range age: 3-7 yr) were investigated by means of ultrasonography, for measuring GET, and by electrogastrography (EGG); 70 children served as controls. Ten patients had Duchenne muscular dystrophy (DMD) and 10 Becker muscular dystrophy (BMD). GET was significantly more delayed in MD patients (DMD, median: 195 min; range 150-260 min; BMD, median: 197 min; range: 150-250 min) than in controls (median: 150 min; 110-180 min; p < 0.05); it markedly worsened at the follow-up in DMD (median: 270 min; range 170-310 min; p < 0.001 vs controls) but not in BMD patients (median: 205 min; 155-275 min; p < 0.05 vs DMD). Baseline EGG showed a significantly lower prevalence of normal rhythm and significantly higher prevalence of dysrhythmias in both groups of patients as compared to controls (% of normal rhythm: DMD 66.7 +/- 8.2, BMB 67.2 +/- 11.5, controls 85.3 +/- 7.2, p < 0.001; % of tachygastria: DMD 28.4 +/- 8.0, BMB 29.8 +/- 12.3, controls 10.6 +/- 5.1, p < 0.001; % of dominant frequency instability coefficient: DMD 36.1 +/- 6.0, BMB 33.2 +/- 2.9, controls 17.9 +/- 7.1, p < 0.001); furthermore, no difference in fed-to-fasting ratio of the dominant EGG power was found between the two groups and controls (DMD 2.84 +/- 1.27, BMB 2.82 +/- 0.98, controls 3.04 +/- 0.85, ns). However, at the follow-up no significant change in the prevalence of normal rhythm and dysrhythmias occurred in both groups (ns vs baseline values), whereas only DMD patients showed a marked reduction in fed-to-fasting power ratio (0.78 +/- 0.59; p < 0.001 vs controls and BMD; p < 0.05 vs baseline), which correlated with the progressive neuromuscular weakness occurring in DMD subjects (r, 0.75; p < 0.001). In children with MD, there is an early abnormality in gastric motility that is due to deranged regulatory mechanisms, whereas contractile activity of smooth muscle cells seems to be preserved. At the follow-up, DMD patients exhibited a progressive failure in neuromuscular function, which was accompanied by a gastric motility derangement with worsening in GET and in EGG features suggesting an altered function of gastric smooth muscle cells.

Gene-mediated Restoration of Normal Myofiber Elasticity in Dystrophic Muscles

Individuals with Duchenne muscular dystrophy (DMD) frequently develop sleep-disordered breathing. Noninvasive ventilation is often prescribed for sleep-disordered breathing treatment based on the American Academy of Sleep Medicine (AASM) criteria. In 2018, DMD disease-specific criteria for sleep-disordered breathing were established. Our study aimed to examine the clinical interpretation differences using these different criteria. We performed a multicenter, retrospective chart review of children with DMD followed at The Hospital for Sick Children, Toronto, Canada, and Rady Children's Hospital, San Diego, California, who underwent polysomnography from August 1, 2012, to February 29, 2020. Baseline characteristics and polysomnography data were summarized using descriptive statistics. Agreement for the diagnosis of sleep-disordered breathing evaluated by kappa statistics and sensitivity/specificity analysis was assessed. One hundred five male children with DMD (mean ± SD age: 12.1 ± 3.8 years; body mass index z score: 0.2 ± 2.3) were included. The proportions of children with DMD that met at least 1 AASM criterion and at least 1 DMD criterion were 45.7% and 67.6%, respectively. We found that 32.4% of children met neither AASM nor DMD criteria. Overall agreement between AASM and DMD criteria was moderate (k = 0.57). There was almost perfect agreement in sleep apnea diagnosis (k = 0.90); however, there was only slight agreement in hypoventilation diagnosis (k = 0.12) between AASM and DMD criteria. There were more children with DMD diagnosed with nocturnal hypoventilation and prescribed noninvasive ventilation using DMD criteria compared with AASM criteria. Future studies should address whether the prescription of noninvasive ventilation for children with DMD based on both criteria is associated with different clinical outcomes. Hurvitz MS, Sunkonkit K, Massicotte C, Li R, Bhattacharjee R, Amin R. Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences? J Clin Sleep Med. 2022;18(2):609-615.

Objective:There is limited and mixed research describing the memory performance of boys with Duchenne muscular dystrophy (DMD), a progressive disorder that affects the muscle and the brain, presumably due to the absence of dystrophin; however, the literature indicates either the existence of a selective deficit in verbal working memory, or more generalized impairment in both verbal and visual memory. Far less is documented about the neurocognitive profile of boys with Becker muscular dystrophy (BMD), a closely related neuromuscular disorder which allows for at least some functional dystrophin protein to circulate. The Child and Adolescent Memory Profile (ChAMP) is a valid and widely used memory battery that has not been studied in either DMD or BMD. This study aimed to assess the verbal and visual memory performance in boys having either a DMD or a BMD diagnosis using the ChAMP. A working memory measure, the Digit Span subtest from the Wechsler Intelligence Scale for Children-Fifth Edition, was also included for comparison.Participants and Methods:Twenty-one patients (Age M = 12.19 ± 3.60; 100% male; 76% DMD, 24% Becker) were selected from retrospective data collection of neuropsychological performance in children with neuromuscular disorders. Patients were recruited and assessed as part of a larger scale IRB-approved research study designed to better understand the neurocognitive and behavioral trajectories of boys with DMD or BMD with a complete neuropsychological battery.Results:Independent samples f-tests revealed no significant differences between groups across verbal (DMD M = 88.71; BMD M = 100.80; p = .08), visual (DMD M =90.36; BMD M 93.60; p = .33), and working memory (DMD M = 84.69; BMD: M 82.60; p = .40) domains. In additional analyses, a one sample f-test comparing verbal and visual memory within DMD children revealed significantly worse verbal than visual memory scores (verbal memory M = 88.71; visual memory M = 90.36; p = &lt;.001).Conclusions:There were no significant differences between groups in verbal, visual, and working memory performance, though sample size was a significant limitation. However, based on a comparison of means, children with BMD appear to have stronger verbal memory skills than children with DMD. Furthermore, significant differences between verbal and visual memory within DMD children were observed, such that verbal memory skills were weaker. These findings add to the absence of literature on verbal and visual memory outcomes in children with DMD and BMD.

CRISPR/Cas9-Mediated Genome Editing Corrects Dystrophin Mutation in Skeletal Muscle Stem Cells in a Mouse Model of Muscle Dystrophy.

Ribosome concentration, ribosome distribution on sucrose density gradients, and in-vitro ribosomal amino-acid incorporation (noncollagen and collagen synthesis) were studied in muscle biopsy samples obtained from 30 patients with Duchenne muscular dystrophy, seven patients with Becker muscular dystrophy, and 10 with facioscapulohumeral muscular dystrophy. Ribosome concentration was normal in Duchenne and facioscapulohumeral and decreased in Becker muscular dystrophy. Distribution of ribosomes in sucrose density gradients showed abnormalities (sharp monosomal peak and fewer polyribosomes) only in Duchenne muscular dystrophy and was normal in the other two types. In-vitro amino-acid incorporation of ribosomes in Duchenne muscular dystrophy revealed high collagen and low noncollagen synthesis of the heavy polyribosomes. This abnormality is controlled by an undetermined enzymatic factor belonging to the soluble enzyme fraction. Supplementation of the dystrophic heavy polyribosomes with normal soluble enzymes restored the synthesis of collagen to that of the controls. Heavy polyribosomes extracted from normals or from carriers produce proportionately more collagen in the presence of soluble enzyme fraction from Duchenne muscular dystrophy than in the presence of their homologous enzymes. In Becker muscular dystrophy, both noncollagen and collagen synthesis of the heavy polyribosomes were increased, under the influence of ribosomal factors. The different protein synthesis in Duchenne and Becker muscular dystrophies suggests that these conditions are non-allelic. In facioscapulohumeral muscular dystrophy the changes in protein synthesis occurred only in the early stage of the disease and consisted of increased noncollagen synthesis of the light polyribosomes, while the heavy polyribosomes had normal activity including collagen synthesis. This reaction was controlled by ribosomal factors.

Research Article| January 01 2010 Delayed Diagnosis of Duchenne Muscular Dystrophy AAP Grand Rounds (2010) 23 (1): 3. https://doi.org/10.1542/gr.23-1-3 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Delayed Diagnosis of Duchenne Muscular Dystrophy. AAP Grand Rounds January 2010; 23 (1): 3. https://doi.org/10.1542/gr.23-1-3 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: delayed diagnosis, duchenne's muscular dystrophy Source: Ciafaloni E, Fox DJ, Mathews KD, et al. Delayed diagnosis in Duchenne muscular dystrophy: data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). J Pediatr. 2009; 155(3): 380– 385; doi: https://doi.org/10.1016/j.jpeds.2009.02.007Google Scholar Investigators from New York, Iowa, Arizona, and Colorado collaborated in a study to assess delay in diagnosis of Duchenne muscular dystrophy (DMD) in patients without a known family history. Study patients were identified using a four-state registry system established by the Muscular Dystrophy Surveillance, Tracking and Research Network. Initially, records of 453 children diagnosed with either Duchenne or Becker muscular dystrophy, born since 1982, were reviewed. Patients classified as having definite or probable DMD, without a known family history prior to birth, were included in the analysis. Abstracted information from patient records included place of birth; residential history; growth data; symptoms; diagnostic tests; disease effects on pulmonary, cardiac and musculoskeletal systems; clinical treatment; and changes in mobility and function over time. The final data set included a cohort of 156 boys with definite or probable DMD. The initial signs and symptoms (SS) of possible DMD in study patients were noted by parents or caregivers at a mean age of 2.5 years. In 28% of these boys the first SS were noted before 1.5 years of age; 58% had SS prior to the age of 3 years. The most frequent SS were motor delay and muscle weakness. There was an average delay of over one year before boys with SS were taken to a health care professional for evaluation. The mean age at which concerns about the initial SS led to a clinical evaluation of the child was 3.6 years. The initial evaluation of the SS by a health care provider included a serum creatine kinase (CK) test in only 35% of cases. For the entire cohort of nonfamilial patients with DMD, the mean age for obtaining the first serum CK was 4.7 years. Between 1982 and 2000, the age at which care providers obtained the first CK in boys with nonfamilial DMD remained unchanged. Overall, there was a delay of about 2.5 years between the onset of DMD symptoms and the time of diagnosis. The authors conclude that there is a significant time lag between onset of SS and diagnosis of DMD and recommend that a CK test be a standard tool in the assessment of developmental delay in boys. DMD, the most common muscular dystrophy in children, is an X-linked recessive disorder occurring in 1 of every 3,500 male newborns,1 resulting from an absence of an essential transmembrane muscle protein. Thirty percent of cases arise from spontaneous mutation in the dystrophin gene. The diagnosis should be suspected in boys with motor difficulties. Global developmental delay does not exclude the diagnosis of DMD as cognitive, behavioral, and language abnormalities are found in one third of cases.2 An elevated serum CK level is a sensitive marker for early detection of DMD.... You do not currently have access to this content.

A manifesting female carrier of Duchenne muscular dystrophy: Importance of genetics for the dystrophinopathies.

Genetic Complementation of Human Muscle Cells via Directed Stem Cell Fusion