Pre-clinical drug tests in the mdx mouse as a model of dystrophinopathies: an overview.
Year: 2012
Type: article
Abstract: Duchenne muscular dystrophy is a lethal X-linked muscle disease affecting 1/3500 live male birth. It results from defects in the subsarcolemmal protein dystrophin, a component of the dystrophin-glycoprotein complex (DGC) which links the intracellular cytoskeleton to the extracellular matrix. The absence of dystrophin leads to muscle membrane fragility, muscle necrosis and gradual replacement of skeletal muscle by fat and connective tissue, through a complex and still unclear cascade of interconnecting events. No cure is currently available, with glucocorticoids being the sole drugs in clinical use in spite of their remarkable side effects. A great effort is devoted at performing pre-clinical tests on the mdx mouse, the mostly used homologous animal model for DMD, with the final aim to identify drugs safer than steroids and able to target the pathogenic mechanisms so to delay pathology progression. This review updates the efforts on this topic, focusing on the open issues about the animal model and highlighting the classes of pharmaceuticals that are more promising as disease-modifiers, while awaiting for more corrective therapies. Although caution is necessary in data transfer from mdx model to DMD patients, the implementation of standard operating procedures and the growing understanding of the pathology may allow a more accurate evaluation of therapeutics, alone or in combination, in pre-clinical settings. A continuous cross-talk with clinicians and patients associations are also crucial points for proper translation of data from mouse to bedside.
Source: Europe PMC (PubMed Central)
Author: Annamaria De Luca
Institution: University of Bari Aldo Moro
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W15335465