(-)-Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy.

Introduction: We conducted an open-label study to examine the effects of the flavonoid (-)-epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD).

Methods: Seven participants received (-)-epicatechin 50 mg twice per day for 8 weeks. Pre- and postprocedures included biceps brachii biopsy to assess muscle structure and growth-relevant endpoints by western blotting, mitochondria volume measurement, and cristae abundance by electron microscopy, graded exercise testing, and muscle strength and function tests.

Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy.

Drug development for rare diseases is challenged by small populations and limited data. This makes development of clinical trial protocols difficult and contributes to the uncertainty around whether or not a potential therapy is efficacious. The use of data standards to aggregate data from multiple sources, and the use of such integrated databases to develop statistical models can inform protocol development and reduce the risks in developing new therapies.

Longitudinal pulmonary function testing outcome measures in Duchenne muscular dystrophy: Long-term natural history with and without glucocorticoids.

We describe changes in pulmonary function measures across time in Duchenne muscular dystrophy patients treated with glucocorticoids (GCs) > 1 year compared to GC naïve patients in the Cooperative International Research Group Duchenne Natural History Study, a multicenter prospective cohort study. 397 participants underwent 2799 pulmonary function assessments over a period up to 10 years. Fifty-three GC naïve participants (< 1 month exposure) were compared to 322 subjects with > 1 year cumulative GC treatment.

Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study.

Background: Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy.

Methods: For this prospective cohort study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy at 20 centres in nine countries.

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Duchenne Regulatory Science Consortium Meeting on Disease Progression Modeling for Duchenne Muscular Dystrophy.

The Duchenne Regulatory Science Consortium (D-RSC) was established to develop tools to accelerate drug development for DMD.  The resulting tools are anticipated to meet validity requirements outlined by qualification/endorsement pathways at both the U.S.

Reachable workspace and performance of upper limb (PUL) in duchenne muscular dystrophy.

Introduction: The Kinect-based reachable workspace relative surface area (RSA) is compared with the performance of upper limb (PUL) assessment in Duchenne muscular dystrophy (DMD).

Methods: 29 individuals with DMD (ages: 7-23; Brooke: 1-5) underwent both Kinect-based reachable workspace RSA and PUL assessments. RSAs were also collected from 24 age-matched controls.

Validity and reliability of smartphone magnetometer-based goniometer evaluation of shoulder abduction--A pilot study.

Background: Goniometers are commonly used by physical therapists to measure range-of-motion (ROM) in the musculoskeletal system. These measurements are used to assist in diagnosis and to help monitor treatment efficacy. With newly emerging technologies, smartphone-based applications are being explored for measuring joint angles and movement.

Reachable workspace reflects dynamometer-measured upper extremity strength in facioscapulohumeral muscular dystrophy.

Introduction: It is not known whether a reduction in reachable workspace closely reflects loss of upper extremity strength in facioscapulohumeral muscular dystrophy (FSHD). In this study we aimed to determine the relationship between reachable workspace and quantitative upper extremity strength measures.

Methods: Maximal voluntary isometric contraction (MVIC) testing of bilateral elbow flexion and shoulder abduction by hand-held dynamometry was performed on 26 FSHD and 27 control subjects.

Measuring quality of life in muscular dystrophy.

Objectives: The objectives of this study were to develop a conceptual model of quality of life (QOL) in muscular dystrophies (MDs) and review existing QOL measures for use in the MD population.

Methods: Our model for QOL among individuals with MD was developed based on a modified Delphi process, literature review, and input from patients and patient advocacy organizations. Scales that have been used to measure QOL among patients with MD were identified through a literature review and evaluated using the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) checklist.

Upper extremity 3-dimensional reachable workspace analysis in dystrophinopathy using Kinect.

Introduction: An innovative upper extremity 3-dimensional (3D) reachable workspace outcome measure acquired using the Kinect sensor is applied toward Duchenne/Becker muscular dystrophy (DMD/BMD). The validity, sensitivity, and clinical meaningfulness of this novel outcome measure are examined.

Methods: Upper extremity function assessment (Brooke scale and NeuroQOL questionnaire) and Kinect-based reachable workspace analyses were conducted in 43 individuals with dystrophinopathy (30 DMD and 13 BMD, aged 7-60 years) and 46 controls (aged 6-68 years).

Ataluren treatment of patients with nonsense mutation dystrophinopathy.

Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders.

Methods: Randomized, double-blind, placebo-controlled study; males ≥ 5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks.

Reachable workspace in facioscapulohumeral muscular dystrophy (FSHD) by Kinect.

Introduction: A depth-ranging sensor (Kinect) based upper extremity motion analysis system was applied to determine the spectrum of reachable workspace encountered in facioscapulohumeral muscular dystrophy (FSHD).

Methods: Reachable workspaces were obtained from 22 individuals with FSHD and 24 age- and height-matched healthy controls. To allow comparison, total and quadrant reachable workspace relative surface areas (RSAs) were obtained by normalizing the acquired reachable workspace by each individual's arm length.

Validity, Reliability, and Sensitivity of a 3D Vision Sensor-based Upper Extremity Reachable Workspace Evaluation in Neuromuscular Diseases.

Introduction: One of the major challenges in the neuromuscular field has been lack of upper extremity outcome measures that can be useful for clinical therapeutic efficacy studies. Using vision-based sensor system and customized software, 3-dimensional (3D) upper extremity motion analysis can reconstruct a reachable workspace as a valid, reliable and sensitive outcome measure in various neuromuscular conditions where proximal upper extremity range of motion and function is impaired.

Methods: Using a stereo-camera sensor system, 3D reachable workspace envelope surface area normalized to an individual's arm length (relative surface area: RSA) to allow comparison between subjects was determined for 20 healthy controls and 9 individuals with varying degrees of upper extremity dysfunction due to neuromuscular conditions.

The 6-Minute Walk Test and Person-Reported Outcomes in Boys with Duchenne Muscular Dystrophy and Typically Developing Controls: Longitudinal Comparisons and Clinically-Meaningful Changes Over One Year.

Introduction: Data is currently lacking anchoring a 30-meter longitudinal change in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as a minimal clinically important difference and "clinically meaningful" person-reported outcomes (PROs) at differing levels of ambulatory ability.

Methods: We describe correlation between measures, 1-year change in measures, and correlation of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and determine if minimal clinically important differences (MCID) of PROs contribute to different estimates of 6-minute walk distance (6MWD) change at differing levels of ability.

The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study.

Introduction: Duchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double-blind, placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6-minute walk test (6MWT) and other endpoints.

Methods: Evaluations performed every 6 weeks included the 6-minute walk distance (6MWD), timed function tests (TFTs), and quantitative strength using hand-held myometry.

The cooperative international neuromuscular research group Duchenne natural history study--a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used.

Unlabelled: Contemporary natural history data in Duchenne muscular dystrophy (DMD) is needed to assess care recommendations and aid in planning future trials.

Methods: The Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 individuals, aged 2-28 years, with DMD in a longitudinal, observational study at 20 centers. Assessments obtained every 3 months for 1 year, at 18 months, and annually thereafter included: clinical history; anthropometrics; goniometry; manual muscle testing; quantitative muscle strength; timed function tests; pulmonary function; and patient-reported outcomes/health-related quality-of-life instruments.

The 6-minute walk test and other clinical endpoints in duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study.

Introduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints.

Methods: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate-determined energy expenditure index, and other exploratory endpoints.

The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures.

Unlabelled: introduction: Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies.

Methods: The Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, ages 2-28 years. A comprehensive battery of measures was obtained.

mHealth application for upper extremity range of motion and reachable workspace.

We present mobile health (mHealth) applications utilizing embedded phone sensors as an angle-measuring device for upper-limb range of motion (ROM) and estimation of reachable workspace to assist in evaluation of upper limb functional capacity. Our results show that the phone can record accurate measurements, as well as provide additional functionalities for clinicians.

Upper extremity reachable workspace evaluation with Kinect.

We propose a novel low-cost method for quantitative assessment of upper extremity workspace envelope using Microsoft Kinect camera. In clinical environment there are currently no practical and cost-effective methods available to provide arm-function evaluation in three-dimensional space. In this paper we examine the accuracy of the proposed technique for workspace estimation using Kinect in comparison with a motion capture system.

Development and application of stereo camera-based upper extremity workspace evaluation in patients with neuromuscular diseases.

Background: The concept of reachable workspace is closely tied to upper limb joint range of motion and functional capability. Currently, no practical and cost-effective methods are available in clinical and research settings to provide arm-function evaluation using an individual's three-dimensional (3D) reachable workspace. A method to intuitively display and effectively analyze reachable workspace would not only complement traditional upper limb functional assessments, but also provide an innovative approach to quantify and monitor upper limb function.

Exercise in neuromuscular diseases.

This article reviews the current knowledge regarding the benefits and contraindications of exercise on individuals with neuromuscular diseases (NMDs). Specific exercise prescriptions for individuals with NMDs do not exist because the evidence base is limited. Understanding the effect of exercise on individuals with NMDs requires the implementation of a series of multicenter, randomized controlled trials that are sufficiently powered and use reliable and valid outcome measures to assess the effect of exercise interventions-a major effort for each NMD.

Physical therapy evaluation and management in neuromuscular diseases.

Neuromuscular disorders (NMDs) are a group of myopathic or neuropathic diseases that directly or indirectly affect the functioning of muscle. Physical therapists (PTs) have extensive specialized training in musculoskeletal evaluation and assessment that gives them the tools to meet the significant needs of this population. This article reviews the role of PTs in treating the NMD population with a discussion of available evaluation techniques and interventions and with an effort to differentiate between treatments known to apply to this population and conventional practice of PTs.

Percent-predicted 6-minute walk distance in duchenne muscular dystrophy to account for maturational influences.

We recently described a modified version of the 6-minute walk test (6MWT) for Duchenne muscular dystrophy (DMD) based partly on the American Thoracic Society (ATS) guidelines. This measure has shown reliability, validity and utility as a primary outcome measure in DMD clinical trials. Because loss of muscle function in DMD occurs against the background of normal childhood growth and development, younger children with DMD can show increase in distance walked during 6MWT over ~1 year despite progressive muscular impairment.