Development of Exon Skipping Therapies for Duchenne Muscular Dystrophy: A Critical Review and a Perspective on the Outstanding Issues

Nucleic Acid Ther. 2017 Oct;27(5):251-259. doi: 10.1089/nat.2017.0682. Epub 2017 Aug 10.


Duchenne muscular dystrophy (DMD) is a rare, severe, progressive muscle-wasting disease leading to disability and premature death. Patients lack the muscle membrane-stabilizing protein dystrophin. Antisense oligonucleotide (AON)-mediated exon skipping is a therapeutic approach that aims to induce production of partially functional dystrophins. Recently, an AON targeting exon 51 became the first of its class to be approved by the United States regulators [Food and Drug Administration (FDA)] for the treatment of DMD. A unique aspect of the exon-skipping approach for DMD is that, depending on the size and location of the mutation, different exons need to be skipped. This challenge raises a number of questions regarding the development and regulatory approval of those individual compounds. In this study, we present a perspective on those questions, following a European stakeholder meeting involving academics, regulators, and representatives from industry and patient organizations, and in the light of the most recent scientific and regulatory experience.

Keywords: exon skipping; oligonucleotides; regulatory approval.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Approval*
  • Dystrophin / genetics*
  • Exons / genetics*
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Muscular Dystrophy, Duchenne / therapy*
  • Mutation
  • Oligonucleotides, Antisense / therapeutic use*
  • Stakeholder Participation
  • United States
  • United States Food and Drug Administration


  • Dystrophin
  • Oligonucleotides, Antisense