2025/07/01 by Dina Mikimoto · 1 voice
Biochemistry, Genetics and Molecular Biology · #Muscle Physiology and Disorders
paper · doi:10.1242/dmm.052561
openalex publication_date 2025/07/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/05/06
Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder that primarily affects boys. It is caused by mutations in the gene encoding dystrophin, a protein essential for maintaining the structural integrity of skeletal and cardiac muscles through their connection to the surrounding extracellular matrix. Symptoms of the condition become noticeable at around two to three years of age and gradually progress, leading to reliance on a wheelchair during teenage years and premature death from cardiorespiratory failure in the second or third decade of life. Although several promising treatments are currently in clinical trials, there is no cure for DMD.The progression of the disease is usually monitored by functional assessments that track changes in mobility and quality of life. However, guidelines for conducting these tests are not well-defined for animal models, resulting in high variability depending on the assessor. To address this problem, Kamila Karimjee and colleagues focused on identifying suitable biomarkers for planned preclinical trials by using the DE50-MD canine model of DMD. In contrast with commonly used mouse models (that exhibit a milder version of the disorder), canine models of DMD more closely reflect the human condition, making them more clinically relevant. The model used in this study carries a spontaneous splice-site mutation resulting in deletion of exon 50 within dystrophin transcripts – which is central to the hotspot for human DMD mutations – and exhibits typical features of muscular dystrophy, including progressive muscle weakness, muscle fibrosis and skeletal muscle wasting. To reduce manual effort and the data bias related to the involvement of the assessor, Kamila Karimjee and colleagues proposed using collar-based accelerometers integrated with their acceleration threshold-based metrics, to quantify changes in activity patterns during disease progression. Because the proposed approach is non-invasive and can be carried out on dogs remaining in their usual environment, it minimises human influence on results and enables a longer-term assessment of the animals' capacity for movement. Moreover, the acceleration threshold method enables the distinction between time spent at different intensity levels of activity, which is not only useful in assessing the effect of investigated treatment on functional outcomes and overall quality of life but also allows comparing results between studies and ensures reproducibility of the work. Kamila Karimjee and colleagues also demonstrated that their approach enables the collection of data during long-term activity monitoring. This allows for discrimination between genotypes and may be applicable for other canine models of DMD, and even in other animal models of diseases associated with locomotor or neuromuscular dysfunction.