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Advances in genetic therapeutic strategies for Duchenne muscular dystrophy

NEW FINDINGS: What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mech...

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Autores principales: Guiraud, Simon, Chen, Huijia, Burns, David T., Davies, Kay E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973818/
https://www.ncbi.nlm.nih.gov/pubmed/26140505
http://dx.doi.org/10.1113/EP085308
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author Guiraud, Simon
Chen, Huijia
Burns, David T.
Davies, Kay E.
author_facet Guiraud, Simon
Chen, Huijia
Burns, David T.
Davies, Kay E.
author_sort Guiraud, Simon
collection PubMed
description NEW FINDINGS: What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X‐linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene‐replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re‐establish muscle function.
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spelling pubmed-49738182016-08-17 Advances in genetic therapeutic strategies for Duchenne muscular dystrophy Guiraud, Simon Chen, Huijia Burns, David T. Davies, Kay E. Exp Physiol Review Articles NEW FINDINGS: What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X‐linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene‐replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re‐establish muscle function. John Wiley and Sons Inc. 2015-12-01 2015-08-04 /pmc/articles/PMC4973818/ /pubmed/26140505 http://dx.doi.org/10.1113/EP085308 Text en © 2015 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Articles
Guiraud, Simon
Chen, Huijia
Burns, David T.
Davies, Kay E.
Advances in genetic therapeutic strategies for Duchenne muscular dystrophy
title Advances in genetic therapeutic strategies for Duchenne muscular dystrophy
title_full Advances in genetic therapeutic strategies for Duchenne muscular dystrophy
title_fullStr Advances in genetic therapeutic strategies for Duchenne muscular dystrophy
title_full_unstemmed Advances in genetic therapeutic strategies for Duchenne muscular dystrophy
title_short Advances in genetic therapeutic strategies for Duchenne muscular dystrophy
title_sort advances in genetic therapeutic strategies for duchenne muscular dystrophy
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973818/
https://www.ncbi.nlm.nih.gov/pubmed/26140505
http://dx.doi.org/10.1113/EP085308
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