Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause ce...

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Bibliographic Details
Published in:Annals of the Indian Academy of Neurology 2018-01, Vol.21 (1), p.3-8
Main Author: Verma, Ashok
Format: Article
Language:English
Subjects:
Amyotrophic lateral sclerosis
Antisense oligonucleotides
Cell death
Clinical trials
Deoxyribonucleic acid
Development and progression
DNA
Duchenne's muscular dystrophy
Dystrophy
eteplirsen
Gene expression
Gene mutation
Gene therapy
Genetic aspects
Health aspects
Hybridization
Laboratories
Mitochondria
Muscular dystrophy
Neuromuscular diseases
nusinersen
oligonucleotide
Proteins
Review
Ribonucleic acid
RNA
Spinal muscular atrophy
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Description
Summary:Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause cell death, and strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO) can recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their safety and target delivery, and scientific controlled clinical trials to ascertain their therapeutic safety and efficacy have led to an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. Over the past 1 year, for the first time, the United States Food and Drug Administration has approved two ASO therapies in genetic neuromuscular diseases. This overview summarizes the recent advances in ASO technology, evolution and use of synthetic ASOs as a therapeutic platform, and the mechanism of ASO action by exon-skipping in Duchenne muscular dystrophy and exon-inclusion in spinal muscular atrophy, with comments on their advantages and limitations.
ISSN:0972-2327
1998-3549
DOI:10.4103/aian.AIAN_298_17