BACKGROUND: Despite the increasing availability of clinical trials in Duchenne muscular dystrophy, racial/ethnic minorities and other populations facing health disparities remain underrepresented in clinical trials evaluating products for Duchenne. We sought to understand the barriers faced by Hispanic/Latino families specifically and underrepresented groups more generally to clinical trial participation in Duchenne.
METHODS: We engaged two participant groups: Hispanic/Latino caregivers of children with Duchenne in the US, including Puerto Rico, and health professionals within the broader US Duchenne community. Caregiver interviews explored attitudes towards and experiences with clinical trials, while professional interviews explored barriers to clinical trial participation among socio-demographically underrepresented families (e.g., low income, rural, racial/ethnic minority, etc.). Interviews were analyzed aggregately and using a thematic analysis approach. An advisory group was engaged throughout the course of the study to inform design, conduct, and interpretation of findings generated from interviews.
RESULTS: Thirty interviews were conducted, including with 12 Hispanic/Latina caregivers and 18 professionals. We identified barriers to clinical trial participation at various stages of the enrollment process. In the initial identification of patients, barriers included lack of awareness about trials and clinical trial locations at clinics that were less likely to serve diverse patients. In the prescreening process, barriers included ineligibility, anticipated non-compliance in clinical trial protocols, and language discrimination. In screening, barriers included concerns about characteristics of the trial, as well as mistrust/lack of trust. In consent and recruitment, barriers included lack of timely decision support, logistical factors (distance, time, money), and lack of translated study materials.
CONCLUSIONS: Numerous barriers hinder participation in Duchenne clinical trials for Hispanic/Latino families and other populations experiencing health disparities. Addressing these barriers necessitates interventions across multiple stages of the clinical trial enrollment process. Recommendations to enhance participation opportunities include developing clinical trial decision support tools, translating prominent clinical trials educational resources such as ClinicalTrials.gov, fostering trusting family-provider relationships, engaging families in clinical trial design, and establishing ethical guidelines for pre-screening potentially non-compliant patients.

OBJECTIVE: Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak.
METHODS: This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models.
RESULTS: One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant.
CONCLUSIONS: Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.

BACKGROUND: Studies have reported health-related quality-of-life impacts of Duchenne muscular dystrophy (DMD); however, further research is needed to understand how those with DMD experience their condition and how psychosocial impacts evolve over time in response to disease progression. This qualitative study explores the social and emotional implications of key transitions, challenges and adaptations throughout the disease course from the perspective of patients and family caregivers.
METHODS: Semi-structured interviews were conducted with men and boys with DMD, and/or their caregivers, in the USA. Thematic analysis was used to examine patterns in data collected across the interviews.
RESULTS: Nineteen participants were included. Three major themes were identified: (1) barriers to participation are multifaceted; (2) an emotional journey shaped by \'inevitable progression;\' (3) family provides critical tangible and emotional support. This study illustrates that psychosocial impacts of DMD are shaped by knowledge of the condition\'s natural history alongside other factors including the extent of social barriers, personal growth and adaptation, and family support.
CONCLUSIONS: Findings provide insight into the strength and resilience with which individuals and their families respond to daily challenges and major clinical milestones and highlight the relative importance of loss of upper limb function as a transition in DMD affecting health-related quality-of-life.

BACKGROUND: Functional activities are extensively used in motor assessments of patients with Duchenne muscular dystrophy. The role of timed items has been reported as an early prognostic factor for disease progression. However, there are two functional activities that are not widely assessed in clinical practice among Duchenne muscular dystrophy patients: rolling and bed rising. This study aimed to investigate whether the 360-degree roll (roll) and supine to sit-to-edge (bed rise) measurements are feasible tools reflecting the functional status of ambulatory DMD children by establishing possible correlations between validated measures: the Vignos Scale (VS), timed rise from floor and the 6-Minute Walk Test (6MWT).
METHODS: A total of 32 ambulant boys with DMD were assessed using timed items, the 6MWT and VS.
RESULTS: The roll and bed rise are correlated with each other. The 6MWT, the floor rise and VS are correlated with the roll and with the bed rise.
CONCLUSIONS: Findings offer preliminary empirical evidence addressing feasibility and safety of roll and bed rise measurements. There is a potential clinical utility of these tests in assessing functional status of DMD ambulant patients.

UNASSIGNED: Duchenne muscular dystrophy (DMD) is a devastating X-linked muscle disease. Clinical evaluation of DMD uses patient-intensive motor function tests, and the recent development of wearable devices allows the collection of a variety of biometric information, including physical activity.
UNASSIGNED: In this study, we examined differences in physical activity and heart rate variability (HRV) between patients with DMD and healthy subjects using a wearable device, and investigated any association between these parameters and motor function in patients with DMD.
UNASSIGNED: Participants were 7 patients with DMD and 8 healthy males, whose physical activity and HRV were provided by a wearable device. These data were used to investigate the relationship between both physical activity and HRV parameters and timed motor functional tests [Time to stand from supine, 10-meter walking time (10MWT), North Star Ambulatory Assessment (NSAA), and 6-minute walking test (6MWT)] in patients with DMD.
UNASSIGNED: Results of 24-hours physical activity, fat burning, total number of steps and active distance, average step rate, average exercise intensity during walking, exercise, degree of forward lean during walking, maximum heart rate, normalized low frequency power (LF norm), and maximum exercise intensity in patients with DMD were lower than those in control subjects. Physical activity and HRV parameters did not correlate with the time to stand from supine. The 10MWT positively correlated with average heart rate, while NSAA negatively correlated with average heart rate, total frequency power (TF), and very low frequency power (VLF) during arousal. The 6MWT negatively correlated with ratio LF/high frequency power (HF).
UNASSIGNED: Physical activity and HRV indices that differ from those of normal children and that correlate with motor function assessment may serve as digital biomarkers.

Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by dystrophin gene deletions (75%), duplications (15-20%) and point mutations (5-10%), a small portion of which are nonsense mutations. Women carrying dystrophin gene mutations are commonly unaffected because the wild X allele may produce a sufficient amount of the dystrophin protein. However, approximately 8-10% of them may experience muscle symptoms and 50% of those over 40 years develop cardiomyopathy. The presence of symptoms defines the individual as an affected \"symptomatic or manifesting carrier\". Though there is no effective cure for DMD, therapies are available to slow the decline of muscle strength and delay the onset and progression of cardiac and respiratory impairment. These include ataluren for patients with nonsense mutations, and antisense oligonucleotides therapies, for patients with specific deletions. Symptomatic DMD female carriers are not included in these indications and little data documenting their management, often entrusted to the discretion of individual doctors, is present in the literature. In this article, we report the clinical and instrumental outcomes of four symptomatic DMD carriers, aged between 26 and 45 years, who were treated with ataluren for 21 to 73 months (average 47.3), and annually evaluated for muscle strength, respiratory and cardiological function. Two patients retain independent ambulation at ages 33 and 45, respectively. None of them developed respiratory involvement or cardiomyopathy. No clinical adverse effects or relevant abnormalities in routine laboratory values, were observed.

BACKGROUND: Duchenne muscular dystrophy, the most common childhood muscular dystrophy, is caused by dystrophin deficiency. Preclinical and phase 2 study data have suggested that givinostat, a histone deacetylase inhibitor, might help to counteract the effects of this deficiency. We aimed to evaluate the safety and efficacy of givinostat in the treatment of Duchenne muscular dystrophy.
METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 trial was done at 41 tertiary care sites in 11 countries. Eligible participants were ambulant, male, and aged at least 6 years, had a genetically confirmed diagnosis of Duchenne muscular dystrophy, completed two four-stair climb assessments with a mean of 8 s or less (≤1 s variance), had a time-to-rise of at least 3 s but less than 10 s, and had received systemic corticosteroids for at least 6 months. Participating boys were randomly assigned (2:1, allocated according to a list generated by the interactive response technology provider) to receive either oral givinostat or matching placebo twice a day for 72 weeks, stratified by concomitant steroid use. Boys, investigators, and site and sponsor staff were masked to treatment assignment. The dose was flexible, based on weight, and was reduced if not tolerated. Boys were divided into two groups on the basis of their baseline vastus lateralis fat fraction (VLFF; measured by magnetic resonance spectroscopy): group A comprised boys with a VLFF of more than 5% but no more than 30%, whereas group B comprised boys with a VLFF of 5% or less, or more than 30%. The primary endpoint compared the effects of givinostat and placebo on the change in results of the four-stair climb assessment between baseline and 72 weeks, in the intention-to-treat, group A population. Safety was assessed in all randomly assigned boys who received at least one dose of study drug. When the first 50 boys in group A completed 12 months of treatment, an interim futility assessment was conducted, after which the sample size was adapted using masked data from the four-stair climb assessments. Furthermore, the starting dose of givinostat was reduced following a protocol amendment. This trial is registered with ClinicalTrials.gov, NCT02851797, and is complete.
RESULTS: Between June 6, 2017, and Feb 22, 2022, 359 boys were assessed for eligibility. Of these, 179 were enrolled into the study (median age 9·8 years [IQR 8·1-11·0]), all of whom were randomly assigned (118 to receive givinostat and 61 to receive placebo); 170 (95%) boys completed the study. Of the 179 boys enrolled, 120 (67%) were in group A (81 givinostat and 39 placebo); of these, 114 (95%) completed the study. For participants in group A, comparing the results of the four-stair climb assessment at 72 weeks and baseline, the geometric least squares mean ratio was 1·27 (95% CI 1·17-1·37) for boys receiving givinostat and 1·48 (1·32-1·66) for those receiving placebo (ratio 0·86, 95% CI 0·745-0·989; p=0·035). The most common adverse events in the givinostat group were diarrhoea (43 [36%] of 118 boys vs 11 [18%] of 61 receiving placebo) and vomiting (34 [29%] vs 8 [13%]); no treatment-related deaths occurred.
CONCLUSIONS: Among ambulant boys with Duchenne muscular dystrophy, results of the four-stair climb assessment worsened in both groups over the study period; however, the decline was significantly smaller with givinostat than with placebo. The dose of givinostat was reduced after an interim safety analysis, but no new safety signals were reported. An ongoing extension study is evaluating the long-term safety and efficacy of givinostat in patients with Duchenne muscular dystrophy.
BACKGROUND: Italfarmaco.

Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping in these patients has the potential to be highly therapeutic through restoration of full-length dystrophin expression. We conducted a 48-week open label study of casimersen and golodirsen in 3 subjects with an exon 45 or 53 duplication. Two subjects (aged 18 and 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, and cardiac function appeared stable in the 2 subjects in whom they could be evaluated. Dystrophin expression increased from 0.94 % ±0.59% (mean±SD) of normal to 5.1% ±2.9% by western blot. Percent dystrophin positive fibers also rose from 14% ±17% at baseline to 50% ±42% . Our results provide initial evidence that the use of exon-skipping drugs may increase dystrophin levels in patients with single-exon duplications.

UNASSIGNED: Muscular dystrophies other than Duchenne muscular dystrophy (DMD) are genetic diseases characterized by increasing muscle weakness, loss of ambulation, and ultimately cardiac and respiratory failure. There are currently no effective therapeutics available. Having demonstrated the efficacy of a N-163 strain of Aureobasidium Pullulans (Neu-REFIX) produced B-1, 3-1,6-Glucan in pre-clinical and clinical studies of Duchenne muscular dystrophy (DMD) earlier, we assessed the effectiveness of this novel Beta glucan in the other muscular dystrophies in the present study.
UNASSIGNED: In this 60-day study, six patients with muscular dystrophies other than DMD consumed one 8g gel of Neu-REFIX beta-glucan along with their usual standard of care treatment regimen, and their biomarkers of relevance to muscle function such as serum calcium (SC), creatine phosphokinase (CPK), and alkaline phosphatase (ALP) levels along with functional improvement criteria, which is, Medical research council (MRC) scale and North Star Ambulatory assessment (NSAA), assessed at baseline and following the intervention.
UNASSIGNED: After the intervention, the SC levels significantly decreased from a mean baseline value of 9.28 mg/dL to 8.31 mg/dL (p-value = 0.02). With a p-value of 0.29, the mean CPK value dropped from 2192.33 IU/L to 1567.5 IU/L. Following the intervention, the ALP levels dropped from 200.33 to 75.5 U/L (p-value = 0.15). MRC scale improved in three out of six patients. NSAA remained stable. There were no adverse effects.
UNASSIGNED: This study has proven the safety of Neu REFIX beta-glucan food supplement and its efficacy in improving both plasma biomarkers and functional parameters of muscle in a short duration of 2 months. Further validation by evaluation of muscle function for a longer duration is recommended to confirm the efficacy of Neu-REFIX food supplement as a potential adjuvant DMT in muscular dystrophies.

Objective: To explore the characteristics and changes of cardiac injury with age in Duchenne muscular dystrophy (DMD) and its clinical significance. Methods: A prospective cohort study was conducted. The 215 patients diagnosed with DMD in West China Second Hospital from January 2019 to November 2022 and aged from 6 to 18 years were enrolled. Their clinical data, myocardial injury markers, routine electrocardiogram, cardiac magnetic resonance (CMR) and echocardiography were collected. The patients were divided into five age groups: 6-<8, 8-<10, 10-<12, 12-<14 and 14-18 years of age, and matched with healthy boys respectively. Independent sample t test or Mann-Whitney U test was used to compare the clinical data and CMR indexes between DMD patients and controls in all age subgroups, and to compare the value of left ventricular ejection fraction (LVEF) measured by echocardiography and CMR in each subgroup of DMD patitents. Pearson correlation analysis or Spearman correlation analysis was used to explore the relation between the CMR indexes and age in DMD patients. Results: A total of 215 patients with DMD (all male) and 122 healthy boys were included in the study. There were 75 DMD patients and 23 controls in 6-<8 years of age group, 77 DMD and 28 controls in 8-<10 years of age group, 39 DMD and 23 controls in 10-<12 years of age group, 10 DMD and 31 controls in the 12-<14 years of age group, and 14 DMD and 17 controls in 14-18 years of age group. In the DMD patients, the older the age, the lower the levels of creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the 6-<8 years of age group, the CK level was 10 760 (7 800, 15 757) U/L, while in the group of 14-18 years of age, it was 2 369 (1 480, 6 944) U/L. As for CK-MB, it was (189±17) μg/L in the 6-<8 years of age group and (62±16) μg/L in the 14-18 years of age group. Cardiac troponin I remained unchanged in <12 years of age groups, but significantly increased in 12-<14 years of age group, reaching the highest value of 0.112 (0.006, 0.085) μg/L. In the DMD patients, the older the age, the higher the proportion of abnormal electrocardiogram (ECG). In the 6-<8 years of age group, the proportion is 29.3% (22/75), while in the 14-18 years of age group, it was 10/14. Correlation analysis showed that the left ventricular end-diastolic volume index was positively related with age (r=0.18, P=0.015), and the left ventricular stroke volume index and cardiac output index were negatively related with age (r=-0.34 and -0.31, respectively, both P<0.001). In the DMD patients, the older the age, the lower LVEF, with the LVEF decreasing to (49.3±3.1)% in the 14-18 years of age group. The LVEF of DMD cases was significantly lower than that of controls in the age subgroups of 8-<10, 10-<12, 12-<14 and 14-18 years of age groups ((57.9±5.2) % vs. (63.6±0.8)%, 60.7% (55.9%, 61.9%) vs. 63.7% (60.2%, 66.0%), 57.1% (51.8%, 63.4%) vs. 62.1 % (59.5%, 64.5)%, (49.3±3.1) % vs. (61.6±1.3)%, respectively; all P<0.01). In the DMD patients, the older the age, the higher the proportion of positive late gadolinium enhancement (LGE). In the 6-<8 years of age group, it was 22% (11/51), in the 12-<14 years of age group, it was 13/14, and in the 14-18 years of age group, all DMD showed positive LGE. The value of LVEF of DMD cases measured by echocardiography was significantly higher than that measured by CMR in 6-<8 years of age group and 8-<10 years of age group (63.2% (60.1%, 66.4%) vs. 59.1 % (55.4%, 62.9%), and (62.8±5.2) % vs. (57.9±5.2)%, all P<0.001). Conclusion: DMD patients develop cardiac injury in the early stage of the disease, and the incidence of cardiac damage gradually increases with both age and the progression of disease.
目的： 探讨 Duchenne型肌营养不良（DMD）患儿心脏损伤特征随年龄的变化趋势及其临床意义。 方法： 前瞻性队列研究。纳入215例2019年1月至2022年11月于四川大学华西第二医院确诊为DMD、年龄为6~18岁的患儿为研究对象。收集并分析首诊时的基本临床资料、心肌标志物、常规心电图、心脏磁共振成像（CMR）、超声心动图等检查指标。将患儿按年龄分为6~<8岁、8~<10岁、10~<12岁、12~<14岁、14~18岁共5组。对照组纳入122名正常男性儿童匹配DMD患儿相应年龄组。分年龄段对DMD患儿与对照组的一般资料和CMR检查指标进行比较，同时比较各年龄段DMD患儿行超声心动图与CMR评估左心室射血分数（LVEF）的差异，组间比较采用独立样本t检验或Mann-Whitney U检验。采用Pearson或Spearman相关分析法分析DMD患儿CMR检查指标与年龄的相关性。 结果： 纳入215例DMD患儿（均为男童）和122名正常男童。6~<8岁DMD患儿75例，对照组23例；8~<10岁DMD患儿77例，对照组28例；10~<12岁DMD患儿39例，对照组23例；12~<14岁DMD患儿10例，对照组31例；14~18岁DMD患儿14例，对照组17例。DMD患儿年龄越大，肌酸激酶、肌酸激酶同工酶（CK-MB）值越低，6~<8岁组肌酸激酶为10 760（7 800，15 757）U/L，14~18岁组为2 369（1 480，6 944）U/L，6~<8岁组CK-MB为（189±17）μg/L，14~18岁组为（62±16）μg/L；肌钙蛋白I在<12岁各组中变化不明显，但在12~<14岁组有较明显升高，达到最高值0.112（0.006，0.085）μg/L。DMD患儿年龄越大，心电图异常比例越高，6~<8岁组为29.3%（22/75），14~18岁组为10/14。DMD患儿左心室舒张末期容积指数与年龄呈正相关（r=0.18，P=0.015），左心室每搏量指数和心输出量指数均与年龄呈负相关（r=-0.34、-0.31，均P<0.001）。DMD患儿年龄越大，LVEF越低，其中14~18岁组的LVEF低至（49.3±3.1）%。8~<10岁、10~<12岁、12~<14岁、14~18岁组的DMD患儿LVEF值均明显低于对照组［（57.9±5.2）%比（63.6±0.8）%、60.7%（55.9%，61.9%）比63.7%（60.2%，66.0%）、57.1%（51.8%，63.4%）比62.1%（59.5%，64.5%）、（49.3±3.1）%比（61.6±1.3）%，均P<0.05］。DMD患儿年龄越大，钆对比剂延迟强化（LGE）发生率越高，6~<8岁组为22%（11/51），12~<14岁组为13/14，14~18岁组均发生LGE。在6~<8岁组与8~<10岁组，超声心动图测出的LVEF均高于CMR测出的LVEF［63.2%（60.1%，66.4%）比59.1%（55.4%，62.9%）、（62.8±5.2）%比（57.9±5.2）%，均P<0.001］。 结论： DMD患儿在病程早期即存在心脏受累，且随着年龄增加和病程延长，心脏损伤发生率逐渐提高。.