Developments in reading frame restoring therapy approaches for Duchenne muscular dystrophy

Expert Opinion on Biological Therapy, vol. 21, pp. 343–359

Abstract

INTRODUCTION: Exon skipping compounds restoring the dystrophin transcript reading frame have received regulatory approval for Duchenne muscular dystrophy (DMD). Recently, focus shifted to developing compounds to skip additional exons, improving delivery to skeletal muscle, and to genome editing, to restore the reading frame on DNA level. AREAS COVERED: We outline developments for reading frame restoring approaches, challenges of mutation specificity, and optimizing delivery. Also, we highlight ongoing efforts to better detect exon skipping therapeutic effects in clinical trials. Searches on relevant terms were performed, focusing on recent publications (<3 years). EXPERT OPINION: Currently, 3 AONS are approved. Whether dystrophin levels are sufficient to slowdown disease progression needs to be confirmed. Enhancing AON uptake by muscles is currently under investigation. Gene editing is an alternative, but one that involves practical and ethical concerns. Given the field's momentum, we believe the efficiency of frame-restoring approaches will improve.

Authors 2

1. Anne-Fleur E. Schneider Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

2. Annemieke M Aartsma-Rus corresponding Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands