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Animal models with a clinically relevant phenotype remain important for robust evaluation of novel therapeutics for the fatal X-linked genetic disorder Duchenne muscular dystrophy (DMD). Demonstration of functional improvement is crucial for both patients and regulatory authorities. Here, we investigate non-invasive methods to quantify activity changes in DE50-MD dogs. Using collar-based Axivity-AX3 tri-axial accelerometers, we measured activity in affected DE50-MD male dogs (3-8 per age point) and littermate wild-type (WT) male controls (3-13 per age point) at monthly intervals from 3 to 18 months of age. Acceleration vector magnitudes were used to derive a series of activity measures over 24 h. Mixed model analyses were used to examine differences between affected and WT groups at different ages. Activity indicators for DE50-MD dogs were significantly higher for percent time spent at rest (P<0.001) and significantly lower for all other activity indicators (all P<0.05), when compared to age-matched WT dogs. Relatively few animals would be required to detect treatment effects with adequate power using these unbiassed, selected and composite activity measures. Our approach reveals opportunities for cross-model standardisation of activity monitoring.
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http://dx.doi.org/10.1242/dmm.052135 | DOI Listing |
J Neurochem
September 2025
Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Rome, Italy.
Patients with Duchenne muscular dystrophy (DMD) may experience neurobehavioral and cognitive concerns, including psychiatric symptoms, due to the absence of full-length dystrophin (Dp427), frequently accompanied by deficiencies in shorter isoforms. The lack of dystrophin affects neurophysiological processes from the uterine phase, impacting neural circuitry in brain regions such as the prefrontal cortex, hippocampus, and cerebellum. This leads to reduced inhibitory GABAergic transmission and altered hippocampal glutamatergic signaling.
View Article and Find Full Text PDFNeurology
October 2025
Department of Neurology, Leiden University Medical Center, the Netherlands.
Background And Objectives: Slow and highly variable disease progression in Becker muscular dystrophy (BMD) stresses the need to develop sensitive outcome measures for clinical trials. We evaluated responsiveness of different outcome measures in adult patients with BMD over 3 years and explored if the sensitivity of outcome measures can be increased by selecting on phenotype or genotype.
Methods: Genetically confirmed patients with BMD were recruited via the Dutch Dystrophinopathy Database.
Am J Phys Med Rehabil
August 2025
Center for Neuromuscular Disease Child Health and Development, National Hospital Organization, Hokkaido, Medical Center, Japan.
Introduction: Duchenne muscular dystrophy (DMD) management often results in tracheostomies or palliative care deaths.
Methods: Two centers, A in the U.S.
Dev Med Child Neurol
September 2025
Pediatric Neurology Unit, Università Cattolica del Sacro Cuore, Rome, Italy.
Zhonghua Nei Ke Za Zhi
September 2025
Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy caused by mutations in the dystrophin gene, which is divided into presymptomatic, early ambulatory, late ambulatory, early non-ambulatory, and late non-ambulatory stages according to its disease progression. Some patients experience non-progressive cognitive developmental delays in the presymptomatic stage. DMD patients gradually develop osteoporosis, cardiomyopathy, decreased respiratory function, delayed puberty, and gastrointestinal symptoms as the disease progresses.
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