Journal Article

Muscle histological changes in a large cohort of patients affected with Becker muscular dystrophy

Minuti, Elisa, Bettica, Paolo, Moggio, Maurizio, Cazzaniga, Sara, Tiberio, Francesca, Fortunato, Francesco, Ciscato, Patrizia, Mondello, Stefania, Comi, Giacomo P., Zanotti, Simona, Magri, Francesca, Ripolone, Michela, Velardo, Daniele, Sciacco, Monica

2022

Overview

Becker muscular dystrophy (BMD) is a severe X-linked muscle disease. Age of onset, clinical variability, speed of progression and affected tissues display wide variability, making a clinical trial design for drug development very complex. The histopathological changes in skeletal muscle tissue are central to the pathogenesis, but they have not been thoroughly elucidated yet. Here we analysed muscle biopsies from a large cohort of BMD patients, focusing our attention on the histopathological muscle parameters, as fibrosis, fatty replacement, fibre cross sectional area, necrosis, regenerating fibres, splitting fibres, internalized nuclei and dystrophy evaluation. We correlated histological parameters with both demographic features and clinical functional evaluations. The most interesting results of our study are the accurate quantification of fibroadipose tissue replacement and the identification of some histopathological aspects that well correlate with clinical performances. Through correlation analysis, we divided our patients into three clusters with well-defined histological and clinical features. In conclusion, this is the first study that analyses in detail the histological characteristics of muscle biopsies in a large cohort of BMD patients, correlating them to a functional impairment. The collection of these data help to better understand the histopathological progression of the disease and can be useful to validate any pharmacological trial in which the modification of muscle biopsy is utilized as outcome measure.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Analysis / Becker muscular distrophy / Becker muscular dystrophy / Biomedical and Life Sciences / Biomedicine / Biopsy / Cohort Studies / Discriminant analysis / Drug development / Fibrosis / Histology / Humans / Monoclonal antibodies / Muscle biopsies / Muscle, Skeletal - pathology / Muscles / Muscular dystrophy / Muscular Dystrophy, Duchenne - pathology / Musculoskeletal system / Mutation / Neurology / Neurosciences / Pathology / Patients / Proteins / Regeneration / Software / Statistical analysis