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Expert Opinion on Orphan Drugs Volume 4, 2016 - Issue 2
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Review

Prospect of gene therapy for cardiomyopathy in hereditary muscular dystrophy

Yongping YueDepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA
,
Ibrahim M. BinalsheikhDepartment of Child Health, School of Medicine, University of Missouri, Columbia, MO, USA
,
Stacey B. LeachDepartment of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
,
Timothy L. DomeierDepartment of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO, USA
&
Dongsheng DuanDepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA;Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USACorrespondence[email protected]
Pages 169-183 | Received 24 Oct 2015, Accepted 20 Nov 2015, Published online: 17 Dec 2015

References

  • Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.
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• This is the first study demonstrating the potential of micro-dystrophin gene therapy to treat Duchenne cardiomyopathy in an animal model.

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• This study suggests that restoration of calcium homeostasis in the heart is a promising strategy to treat dystrophic cardiomyopathy.

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• This is the first study demonstrating systemic gene delivery in an animal model of muscular dystrophy.

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•• This is the first study demonstrating improvement of cardiac contractility following AAV-mediated micro-dystrophin gene therapy in a model of dilated Duchenne cardiomyopathy.

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• This study demonstrates that AAV micro-dystrophin gene therapy can reduce stress-induced cardiac death in terminal-aged mdx mice.

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• This article provides an excellent review on the cloning of the dystrophin gene.

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• This study demonstraes the importance of dystrophin spectrin-like repeats 16 and 17 for Duchenne muscular dystrophy gene therapy.

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• This study demonstrates for the first time that an abbreviated dystrophin gene may benefit DMD patients.

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•• This study reveals the critical structure-funciton relationship of the dystrophin gene and the implication for Duchenne muscular dystrophy gene therapy.

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  • Gregorevic P, Allen JM, Minami E, et al. rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice. Nat Med. 2006;12(7):787–789.
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•• This study opens the door of systemic AAV gene therapy in a large mammal with muscular dystrophy.

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• This study demonstrates that genetic correction of 50% cardiomyocytes may be sufficient to treat dystrophic cardiomyopathy. This study also demonstrates that aged female mdx mice have dialted cardiomyopathy.

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• This is the first study demonstrating exon-skipping in human patients.

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• This study demonstrates that newly developed tricyclo oligomers can significantly improve exon-skipping in animal models of muscular dystrophy.

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• This study suggests that AAV-mediated exon-skipping can treat dystrophic cardiomyopathy in a large animal model.

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• This study demonstrates the feasiblity of genome editing as a therapy for Duchenne muscular dystrophy.

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• This study reveals the potential of using RNA interference to treat dominant muscular dystrophy.

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• This study demonstrates the therapeutic potential of AAV therapy for limb girdle muscular dystrophy in human patients.

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• This study demonstrates the feasibility of systemic AAV gene therapy to treat heart disease associated with limb girdle muscular dystrophy.

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