Introduction: Duchenne muscular dystrophy (DMD) is an X-linked handicapping disease due to the loss of an essential muscle protein dystrophin. Dystrophin-null animals have been extensively used to study disease mechanisms and to develop experimental therapeutics. Despite decades of research, however, treatment options for DMD remain very limited.Areas covered: High-throughput high-content screening and precision medicine offer exciting new opportunities. Here, the authors review animal models that are suitable for these studies.Expert opinion: Nonmammalian models (worm, fruit fly, and zebrafish) are particularly attractive for cost-effective large-scale drug screening. Several promising lead compounds have been discovered using these models. Precision medicine for DMD aims at developing mutation-specific therapies such as exon-skipping and genome editing. To meet these needs, models with patient-like mutations have been established in different species. Models that harbor hotspot mutations are very attractive because the drugs developed in these models can bring mutation-specific therapies to a large population of patients. Humanized hDMD mice carry the entire human dystrophin gene in the mouse genome. Reagents developed in the hDMD mouse-based models are directly translatable to human patients.
Keywords: AAV; Adeno-associated virus; BMD; Becker muscular dystrophy; CRISPR; DMD; dystrophin; exon-skipping; genome editing; personized therapy.
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