Author's Reply: Standard of care for Duchenne muscular dystrophy in children

2018 ◽  
Vol 66 (2) ◽  
pp. 582
Author(s):  
A Nalini
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Standard Of Care

A Longitudinal Study of Quantitative Muscle Strength and Functional Motor Ability in Ambulatory Boys with Duchenne Muscular Dystrophy

2021 ◽  
pp. 1-14
Author(s):  
Cathleen E. Buckon ◽  
Susan E. Sienko ◽  
Eileen G. Fowler ◽  
Anita M. Bagley ◽  
Loretta A. Staudt ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Strength ◽  
Genetic Disorder ◽  
Knee Extensor ◽  
Standard Of Care ◽  
Rate Of Change ◽  
Isokinetic Dynamometry ◽  
Gross Motor

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder, that is characterized by progressive muscle degeneration and loss of ambulation between 7–13 years of age. Novel pharmacological agents targeting the genetic defects and disease mechanisms are becoming available; however, corticosteroid (CS) therapy remains the standard of care. Objective: The purpose of this longitudinal study was to elucidate the effect of CS therapy on the rate of muscle strength and gross motor skill decline in boys with DMD and assess the sensitivity of selected outcome measures. Methods: Eighty-four ambulatory boys with DMD (49–180 months), 70 on CS, 14 corticosteroid naïve (NCS), participated in this 8-year multi-site study. Outcomes included; isokinetic dynamometry, the Standing (STD) and Walking/Running/jumping (WRJ) dimensions of the Gross Motor Function Measure (GMFM), and Timed Function Tests (TFTs). Nonlinear mixed modeling procedures determined the rate of change with age and the influence of steroids. Results: Despite CS therapy the rate of decline in strength with age was significant in all muscle groups assessed. CS therapy significantly slowed decline in knee extensor strength, as the NCS group declined at 3x the rate of the CS group. Concurrently, WRJ skills declined in the NCS group at twice the rate of the CS group. 4-stair climb and 10 meter walk/run performance was superior in the boys on CS therapy. Conclusion: CS therapy slowed the rate of muscle strength decline and afforded longer retention of select gross motor skills in boys on CS compared to boys who were NCS. Isokinetic dynamometry, Walk/Run/Jump skills, and select TFTs may prove informative in assessing the efficacy of new therapeutics in ambulatory boys with DMD.

Eteplirsen Delays Time to Loss of Ambulation in Patients With Duchenne Muscular Dystrophy Compared With Patients Receiving Standard of Care

2019 ◽  
Author(s):  
André Müller-York ◽  
Joel Iff ◽  
Charles Gerrits ◽  
Gautam Sajeev ◽  
James Signorovitch ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Standard Of Care

scholarly journals Use of air stacking to improve pulmonary function in Indonesian Duchenne muscular dystrophy patients: bridging the standard of care gap in low middle income country setting

2019 ◽  
Vol 13 (S11) ◽  
Author(s):  
Kristy Iskandar ◽  
Sunartini ◽  
Andika Priamas Nugrahanto ◽  
Nissya Ilma ◽  
Alvin Santoso Kalim ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Pulmonary Function ◽  
Early Stage ◽  
Standard Of Care ◽  
Assisted Ventilation ◽  
Manual Ventilation ◽  
Predictive Values ◽  
Respiratory Management ◽  
Respiratory Devices

Abstract Background Duchenne Muscular Dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease, characterized by progressive loss of muscle strength. Respiratory failure is the main cause of morbidity and mortality in DMD patients. Respiratory devices have been reported to increase the effectiveness of cough and pulmonary function, thus prolong the survival rate. However, there is scarcity of studies about DMD patients’ respiratory profiles and usage of respiratory devices in Indonesia. Methods We recruited 8 Indonesian DMD patients in Dr. Sardjito Hospital and UGM Academic Hospital, Yogyakarta. Baseline pulmonary function was measured using spirometry. Peak Cough Flow was measured at baseline, with chest compression, after air stacking with manual ventilation bag, and with the combined techniques. Data recorded was presented as mean ± SD and analysed using ANOVA. Results Here we show the respiratory profiles from 8 non-ambulatory DMD patients (mean age: 13.25 ± 3.96 years old) confirmed by genetic testing. None of them had access to respiratory devices. Spirometry measurements showed 7 of 8 patients had severe restrictive pulmonary function with mean FEV1/FVC 22.40 ± 10.30% of predictive values (normal ratio > 70%). In addition, all patients showed poor cough performances measured by peak cough flowmeter (160 ± 44.58 L/min (normal value > 270 L/min)) that were improved by air stacking using a manual ventilation bag (167.4 ± 46.72 L/min). Three patients who had nocturnal hypoventilation did not have daytime hypercapnia. Manual ventilation bag or mechanical in−/ex-sufflation was indicated in 75% of patients while nocturnal assisted ventilation was indicated in 50% of patients. Neither daytime assisted ventilation nor tracheostomy was indicated in these patients. Conclusion Use of manual exsufflation in combination with the manual ventilation bag for air stacking to improve cough performance is recommended as the first step of respiratory management in DMD patients. Provision of manual ventilation bag serve as an affordable and effective device for respiratory support in the early stage of respiratory involvement in those non-ambulatory patients with DMD.

scholarly journals Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients

2021 ◽  
Author(s):  
Craig M McDonald ◽  
Francesco Muntoni ◽  
Vinay Penematsa ◽  
Joel Jiang ◽  
Allan Kristensen ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Nonsense Mutation ◽  
Vital Capacity ◽  
Standard Of Care ◽  
Phase Iii ◽  
History Of ◽  
Phase Iii Study

Aim: We investigated the effect of ataluren plus standard of care (SoC) on age at loss of ambulation (LoA) and respiratory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) versus patients with DMD on SoC alone. Patients & methods: Study 019 was a long-term Phase III study of ataluren safety in nmDMD patients with a history of ataluren exposure. Propensity score matching identified Study 019 and CINRG DNHS patients similar in disease progression predictors. Results & conclusion: Ataluren plus SoC was associated with a 2.2-year delay in age at LoA (p = 0.0006), and a 3.0-year delay in decline of predicted forced vital capacity to <60% in nonambulatory patients (p = 0.0004), versus SoC. Ataluren plus SoC delays disease progression and benefits ambulatory and nonambulatory patients with nmDMD. ClinicalTrials.gov: NCT01557400 .

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.

scholarly journals Advances in Pulmonary Care in Duchenne Muscular Dystrophy

US Neurology ◽  
2017 ◽  
Vol 13 (01) ◽  
pp. 35 ◽  
Author(s):  
Oscar H Mayer ◽  
Erik K Henricson ◽  
Craig M McDonald ◽  
Gunnar M Buyse ◽  
◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Pulmonary Function ◽  
Vital Capacity ◽  
Standard Of Care ◽  
Phase Iii ◽  
Progressive Muscle Weakness ◽  
History Of ◽  
Lower Limit Of Normal ◽  
Successful Phase

Duchenne muscular dystrophy (DMD) is a degenerative neuromuscular disease leading to progressive muscle weakness and loss. This review discusses advances in understanding the natural history of DMD, as well as recent pharmacotherapies. Decline in expiratory and inspiratory pulmonary function results in ineffective airway clearance, sleep-disordered breathing and nocturnal and daytime respiratory failure. Routine measures of pulmonary function include forced vital capacity (FVC) and peak expiratory flow (PEF). Both measures follow parallel trajectories and relentlessly decline, reaching the lower limit of normal of 80% of predicted at early teenage years. Moreover, decline in PEF and FVC are closely correlated with respiratory complications and clinically relevant thresholds for FVC are defined in standard of care recommendations. Glucocorticoids (GCs) delay the onset of pulmonary function decline, but once patients have reached the 80% of predicted threshold the decline of FVC and PEF in GC users and patients not using GCs is comparable. In the successful phase III DELOS trial in DMD patients not using GCs, the short-chain benzoquinone idebenone (Raxone®, Santhera Pharmaceuticals, Liestal, Switzerland) has demonstrated statistically significant and clinically relevant efficacy on expiratory and inspiratory function in patients in the pulmonary function decline stage. These results indicate that idebenone can modify the natural course of respiratory disease progression, which is relevant in clinical practice where loss of respiratory function continues to be a predominant cause of early morbidity and mortality in DMD.

scholarly journals Prednisolone rescues Duchenne muscular dystrophy phenotypes in human pluripotent stem cell–derived skeletal muscle in vitro

2021 ◽  
Vol 118 (28) ◽  
pp. e2022960118
Author(s):  
Ziad Al Tanoury ◽  
John F. Zimmerman ◽  
Jyoti Rao ◽  
Daniel Sieiro ◽  
Harold M. McNamara ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Premature Death ◽  
Standard Of Care ◽  
Beneficial Effects ◽  
Glycoprotein Complex ◽  
Optimized Protocol ◽  
Vitro Model ◽  
Induced Pluripotent

Duchenne muscular dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced pluripotent stem cells (iPSC) to a late myogenic stage. This allows us to recapitulate classical DMD phenotypes (mislocalization of proteins of the dystrophin-associated glycoprotein complex, increased fusion, myofiber branching, force contraction defects, and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion, and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are caused by antiinflammatory properties. Our work introduces a human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.

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