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Advances in genetic therapeutic strategies for Duchenne muscular dystrophy

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1113/EP085308

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Oxford college:
Hertford College
Role:
Author
ORCID:
0000-0001-8807-8520


Publisher:
Wiley
Journal:
Experimental Physiology More from this journal
Volume:
100
Issue:
12
Pages:
1458-1467
Publication date:
2015-07-03
Acceptance date:
2015-07-01
DOI:
EISSN:
1469-445X
ISSN:
0958-0670
Pmid:
26140505


Language:
English
Keywords:
Pubs id:
pubs:531657
UUID:
uuid:eb2b677a-ba19-4e68-93e0-301f37152e43
Local pid:
pubs:531657
Source identifiers:
531657
Deposit date:
2018-10-11

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