A new line of dystrophic mdx mice on the DBA/2J (D2) background has emerged as a candidate to study the efficacy of therapeutic approaches for Duchenne muscular dystrophy (DMD). These mice harbor genetic polymorphisms that appear to increase the severity of the dystropathology, with disease modifiers that also occur in DMD patients, making them attractive for efficacy studies and drug development. This workshop aimed at collecting and consolidating available data on the pathological features and the natural history of these new D2/mdx mice, for comparison with classic mdx mice and controls, and to identify gaps in information and their potential value. The overall aim is to establish guidance on how to best use the D2/mdx mouse model in preclinical studies.
ObjectiveTo evaluate the sensitivity of electrical impedance myography (EIM) to disease progression in both ambulatory and non‐ambulatory boys with DMD.Methods and ParticipantsA non‐blinded, longitudinal cohort study of 29 ambulatory and 15 non‐ambulatory boys with DMD and age‐similar healthy boys. Subjects were followed for up to 1 year and assessed using the Myolex® mViewTM EIM system as part of a multicenter study.ResultsIn the ambulatory group, EIM 100 kHz resistance values showed significant change compared to the healthy boys. For example, in lower extremity muscles, the average change in EIM 100 kHz resistance values over 12 months led to an estimated effect size of 1.58. Based on these results, 26 DMD patients/arm would be needed for a 12‐month clinical trial assuming a 50% treatment effect. In non‐ambulatory boys, EIM changes were greater in upper limb muscles. For example, biceps at 100kHz resistance gave an estimated effect size of 1.92 at 12 months. Based on these results, 18 non‐ambulatory DMD patients/arm would be needed for a 12‐month clinical trial assuming a 50% treatment effect. Longitudinal changes in the 100 kHz resistance values for the ambulatory boys correlated with the longitudinal changes in the timed supine‐to‐stand test. EIM was well‐tolerated throughout the study.InterpretationThis study supports that EIM 100 kHz resistance is sensitive to DMD progression in both ambulatory and non‐ambulatory boys. Given the technology’s ease of use and broad age range of utility it should be employed as an exploratory endpoint in future clinical therapeutic trials in DMD.Trial Registration: Clincialtrials.gov registration #NCT02340923
Introduction The Duchenne Video Assessment (DVA) assesses quality of movement as an indication of Duchenne muscular dystrophy (DMD) disease severity. Caregivers video record patients performing home‐based movement tasks using a mobile application, and physical therapists (PTs) rate the videos using scorecards with prespecified compensatory movement criteria. Reliability and construct validity of the DVA were tested using video and Pediatric Outcomes Data Collection Instrument (PODCI) data from patients with DMD and healthy controls from a separate study. Methods Fifteen PTs were trained and certified as DVA raters. All raters scored videos of five subjects performing each movement task; nine raters rescored the same videos four weeks later. Three raters scored videos from an average of 25 subjects for each movement task. Aggregate scores were used to test construct validity. An expert DMD clinician assigned each video to a severity group for known‐groups analyses. Differences between rater scores across severity groups were tested and correlations between DVA and PODCI scores were calculated. Results Inter‐rater reliability (intraclass correlation coefficient [ICC]) between all 15 raters ranged from 0.70 to 0.97 for all movement tasks. Mean intra‐rater reliability ICC for nine raters ranged from 0.82 to 0.98 for all movement tasks. There were statistically significant differences between known severity groups for all movement tasks. The DVA correlated strongly with related PODCI constructs of physical function and weakly with unrelated constructs. Discussion The DVA was found to be a reliable and valid tool for measuring quality of movement as an indication of disease severity.
Background Patients with Duchenne muscular dystrophy (DMD) adopt compensatory movement patterns as muscles weaken. The Duchenne Video Assessment (DVA) measures patient ease of movement through identification of compensatory movement patterns. The DVA directs caregivers to video record patients performing specific movement tasks at home using a secure mobile application, and DVA-certified physical therapists (PTs) score the videos using scorecards with prespecified compensatory movement criteria. The goal of this study was to develop and refine the DVA scorecards. Methods To develop the initial scorecards, 4 PTs collaboratively created compensatory movement lists for each task, and researchers structured the lists into scorecards. A 2-round modified Delphi process was used to gather expert opinion on the understandability, comprehensiveness, and clinical meaningfulness of the compensatory movements on the scorecards. Eight PTs who had evaluated ≥50 patients with DMD and participated in ≥10 DMD clinical trials were recruited for the panel. In Round 1, panelists evaluated compensatory movement criteria understandability via questionnaire and tested the scorecards. In Round 2, panelists participated in an in-person meeting to discuss areas of disagreement from Round 1 and reach consensus (≥75% agreement) on all revisions to the scorecards. Results During the Round 1 revisions to the scorecards, there were 67 changes (44%) to the wording of 153 original compensatory movement criteria and 3 criteria were removed. During the Round 2 revisions to the scorecards, there were 47 changes (31%) to the wording of 150 compensatory movement criteria, 20 criteria were added, and 30 criteria were removed. The panel reached 100% agreement on all changes made to scorecards during Round 2. Conclusion PTs with extensive experience evaluating patients with DMD confirmed that the compensatory movement criteria included in the DVA scorecards were understandable, comprehensive, and clinically meaningful.
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