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Exon-skipping advances for Duchenne muscular dystrophy
- Source :
- Human Molecular Genetics. 27:R163-R172
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- Duchenne muscular dystrophy (DMD) is a fatal genetic disorder characterized by progressive muscle wasting that has currently no cure. Exon-skipping strategy represents one of the most promising therapeutic approaches that aim to restore expression of a shorter but functional dystrophin protein. The antisense field has remarkably progress over the last years with recent accelerated approval of the first antisense oligonucleotide-based therapy for DMD, Exondys 51, though the therapeutic benefit remains to be proved in patients. Despite clinical advances, the poor effective delivery to target all muscle remains the main hurdle for antisense drug therapy. This review describes the antisense-based exon-skipping approach for DMD, from proof-of-concept to first marketed drug. We discuss the main obstacles to achieve a successful exon-skipping therapy and the latest advances of the international community to develop more powerful chemistries and more sophisticated delivery systems in order to increase potency, bioavailability and safety. Finally, we highlight the importance of collaborative efforts and early dialogue between drug developers and regulatory agencies in order to overcome difficulties, find appropriate outcome markers and collect useful data.
- Subjects :
- 0301 basic medicine
Drug
RNA Splicing
Duchenne muscular dystrophy
media_common.quotation_subject
Bioinformatics
Morpholinos
Dystrophin
03 medical and health sciences
Pharmacotherapy
Genetics
medicine
Animals
Humans
RNA, Antisense
Muscular dystrophy
Molecular Biology
Wasting
Genetics (clinical)
media_common
biology
Genetic disorder
Exons
Genetic Therapy
General Medicine
Oligonucleotides, Antisense
medicine.disease
Exon skipping
Muscular Dystrophy, Duchenne
Alternative Splicing
030104 developmental biology
biology.protein
medicine.symptom
Subjects
Details
- ISSN :
- 14602083 and 09646906
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....659258da2a8633380a4942d6324b6eb0