Micro-utrophin improves cardiac and skeletal muscle function of severely affected D2/mdx mice

Journal article

Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by mutations in the dystrophin gene. DMD boys are wheelchair-bound around 12 years and generally survive into their twenties. There is currently no effective treatment except palliative care, although personalized treatments such as exon skipping, stop codon read-through, and viral-based gene therapies are making progress. Patients present with skeletal muscle pathology, but most also show cardiomyopathy by the age of 10. A systemic therapeutic approach is needed that treats the heart and skeletal muscle defects in all patients. The dystrophin-related protein utrophin has been shown to compensate for the lack of dystrophin in the mildly affected BL10/mdx mouse. The purpose of this investigation was to demonstrate that AAV9-mediated micro-utrophin transgene delivery can not only functionally replace dystrophin in the heart, but also attenuate the skeletal muscle phenotype in severely affected D2/mdx mice. The data presented here show that utrophin can indeed alleviate the pathology in skeletal and cardiac muscle in D2/mdx mice. These results endorse the view that utrophin modulation has the potential to increase the quality life of all DMD patients whatever their mutation.

Authors: Kennedy, T; Guiraud, S; Edwards, B; Squire, S; Moir, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Molecular Therapy - Methods and Clinical Development
• Volume: 11
• Pages: 92-105
• Publication date: 2018-10-16
• Acceptance date: 2018-10-08
• DOI: 10.1016/j.omtm.2018.10.005
• EISSN: 2329-0501
• Pmid: 30417024
• Language: English
• Keywords: cardiac cine-MRI; utrophin; cardiomyopathy; D2/mdx; AAV; duchenne