Yonsei Med J.  2020 Apr;61(4):273-283. 10.3349/ymj.2020.61.4.273.

Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy

Affiliations
  • 1Department of Function, ShiJiaZhuang Traditional Chinese Medical Hospital, ShiJiaZhuang, HeBei, China. liqingliyang@126.com

Abstract

The reduction of survival motor neuron (SMN) protein causes spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease. Nusinersen is an antisense oligonucleotide, approved by the FDA, which specifically binds to the repressor within SMN2 exon 7 to enhance exon 7 inclusion and augment production of functional SMN protein. Nusinersen is the first new oligonucleotide-based drug targeting the central nervous system for the treatment of SMA. This review of nusinersen will discuss its action mechanism, cellular uptake, trafficking mechanisms, and administration approaches to cross the blood-brain barrier. Furthermore, nusinersen clinical trials will be assessed in terms of pharmacokinetics, tolerability and safety, the clinical outcomes of multiple intrathecal doses, and a discussion on the primary and secondary endpoints.

Keyword

blood-brain barrier; cellular uptake; exon splicing; phosphonothioate antisense oligonucleotides; survival of motor neuron gene; Nusinersen

MeSH Terms

Blood-Brain Barrier
Central Nervous System
Drug Delivery Systems
Exons
Motor Neurons
Muscular Atrophy, Spinal*
Neuromuscular Diseases
Pharmacokinetics
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