Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3-8 |
| Number of pages | 6 |
| Journal | Annals of Indian Academy of Neurology |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2018 |
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Keywords
- Dystrophy
- eteplirsen
- nusinersen
- oligonucleotide
- spinal muscular atrophy
ASJC Scopus subject areas
- Clinical Neurology
Cite this
Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases. / Verma, Ashok.
In: Annals of Indian Academy of Neurology, Vol. 21, No. 1, 01.01.2018, p. 3-8.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases
AU - Verma, Ashok
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Dystrophy
KW - eteplirsen
KW - nusinersen
KW - oligonucleotide
KW - spinal muscular atrophy
UR - http://www.scopus.com/inward/record.url?scp=85044837465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044837465&partnerID=8YFLogxK
U2 - 10.4103/aian.AIAN_298_17
DO - 10.4103/aian.AIAN_298_17
M3 - Review article
AN - SCOPUS:85044837465
VL - 21
SP - 3
EP - 8
JO - Annals of Indian Academy of Neurology
JF - Annals of Indian Academy of Neurology
SN - 0972-2327
IS - 1
ER -