Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

Research output: Contribution to journalReview article

4 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)3-8
Number of pages6
JournalAnnals of Indian Academy of Neurology
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2018

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Neuromuscular Diseases
Inborn Genetic Diseases
Antisense Oligonucleotides
Therapeutics
Exons
Technology
Safety
Gene Expression
Spinal Muscular Atrophy
Mitochondrial Genes
Duchenne Muscular Dystrophy
Poisons
Controlled Clinical Trials
Mutant Proteins
United States Food and Drug Administration
Cause of Death
Proteins
Cell Death
RNA
Genes

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 journalReview article

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