Related Experiment Video
Updated: Nov 23, 2025
Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides
Published on: May 7, 2020
Developing DMD therapeutics: a review of the effectiveness of small molecules, stop-codon readthrough, dystrophin
Omar Sheikh1, Toshifumi Yokota1
1Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, Canada.
Introduction:
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the dystrophin (DMD) gene. Most patients die from respiratory failure or cardiomyopathy. There are significant unmet needs for treatments for DMD as the standard of care is principally limited to symptom relief through treatments including steroids.
Areas Covered:
This review summarizes safety and efficacy in promising areas of DMD therapeutics - small molecules, stop codon readthrough, gene replacement, and exon skipping - under clinical examination from 2015-2020 as demonstrated in the NIH Clinical Trials and PubMed search engines.
Expert Opinion:
Currently, steroids persist as the most accessible medicine for DMD. Stop-codon readthrough, gene replacement, and exon-skipping therapies all aim to restore dystrophin expression. Of these strategies, gene replacement therapy has recently gained momentum while exon-skipping retains great traction. The FDA approval of three exon-skipping antisense oligonucleotides illustrate this regulatory momentum, though the effectiveness and sequence design of eteplirsen remain controversial. Cell-penetrating peptides promise to more efficaciously treat DMD-related cardiomyopathy.The recent success of antisense therapies, however, poses major regulatory challenges. To fully realize the benefits of exon-skipping, including cocktail oligonucleotide-mediated multiple exon-skipping and oligonucleotide drugs for very rare mutations, regulatory challenges need to be addressed in coordination with scientific advances.
Insights
Duchenne muscular dystrophy (DMD) treatments are advancing beyond steroids. Gene replacement and exon-skipping therapies aim to restore dystrophin, with exon-skipping showing regulatory momentum despite ongoing challenges.
Area of Science:
- Neurology
- Genetics
- Pharmacology
Background:
- Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by mutations in the dystrophin gene.
- Current standard care for DMD primarily offers symptom relief, with significant unmet needs for effective treatments.
- Respiratory failure and cardiomyopathy are leading causes of mortality in DMD patients.
Purpose of the Study:
- To review the safety and efficacy of emerging DMD therapeutics.
- To assess clinical trial data for small molecules, stop codon readthrough, gene replacement, and exon skipping therapies.
- To identify trends and challenges in DMD treatment development from 2015-2020.
Main Methods:
- Systematic review of clinical trials and literature.
- Searches conducted in NIH Clinical Trials and PubMed databases.
- Focus on therapeutic strategies under clinical investigation between 2015 and 2020.
Main Results:
- Steroids remain the primary accessible treatment for DMD.
- Gene replacement and exon-skipping therapies aim to restore dystrophin expression, showing promise.
- FDA approval of exon-skipping antisense oligonucleotides indicates regulatory progress, though specific therapies like eteplirsen face scrutiny.
Conclusions:
- Exon-skipping and gene replacement therapies are key strategies for restoring dystrophin.
- Cell-penetrating peptides show potential for treating DMD-related cardiomyopathy.
- Addressing regulatory hurdles is crucial for advancing novel DMD therapies like exon-skipping, especially for rare mutations.
