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Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: Current Status of Therapeutic Approaches
Abstract
Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by progressive muscle weakness, is caused by the absence or a decreased amount of the muscle cytoskeletal protein dystrophin. Currently, several therapeutic approaches to cure DMD are being investigated, which can be categorized into two groups: therapies that aim to restore dystrophin expression, and those that aim to compensate for the lack of dystrophin. Therapies that restore dystrophin expression include read-through therapy, exon skipping, vector-mediated gene therapy, and cell therapy. Of these approaches, the most advanced are the read-through and exon skipping therapies. In 2014, ataluren, a drug that can promote ribosomal read-through of mRNA containing a premature stop codon, was conditionally approved in Europe. In 2016, eteplirsen, a morpholino-based chemical capable of skipping exon 51 in premature mRNA, received conditional approval in the USA. Clinical trials on vector-mediated gene therapy carrying micro- and mini- dystrophin are underway. More innovative therapeutic approaches include CRISPR/Cas9-based genome editing and stem cell-based cell therapies. Here we review the current status of therapeutic approaches for DMD, focusing on therapeutic approaches that can restore dystrophin.
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“Despite considerable efforts, the treatment available for DMD remains supportive rather than curative.”
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“Currently, several therapeutic approaches (gene therapy, cell therapy, and exon skipping) have been investigated to restore the expression of dystrophin in DMD muscles.35,36”
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Metadata
- Authors
- Shimizu-Motohashi, Y., Komaki, H., Motohashi, N., Takeda, S., Yokota, T., & Aoki, Y.
- Affiliations
- Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan
- Translational Medical Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan
- Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, Itabashi, Tokyo, 173-0015, Japan
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan
- Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta. 831 Medical Sciences Building, 8613-114 St., Edmonton, AB T6G 2H7, Canada
- ORCID
- Yokota, Toshifumi
- Venue
- Journal of Personalized Medicine
- Publisher
- MDPI AG
- Published
- 2019-01-07
- Volume
- 9
- Issue
- 1
- Pages
- 1
- ISSN
- 2075-4426
- PMC
- PMC6462907
- Cited by
- 82
- References
- 75
- Language
- en
- Funders
- Japan Society for the Promotion of Science (18K07544)
- Research on Nervous and Mental Disorders (28-6)
- Japan Agency for Medical Research and Development (18ek0109239h0002, 18lm0203066h0001, 18lm0203069h0001)
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