Current Status of Antisense Oligonucleotide-Based Therapy in Neuromuscular Disorders.

Drugs
Flavien BizotAurélie Goyenvalle

Abstract

Neuromuscular disorders include a wide range of diseases affecting the peripheral nervous system, which are primarily characterized by progressive muscle weakness and wasting. While there were no effective therapies until recently, several therapeutic approaches have advanced to clinical trials in the past few years. Among these, the antisense technology aiming at modifying RNA processing and function has remarkably progressed and a few antisense oligonucleotides (ASOs) have now been approved. Despite these recent clinical successes, several ASOs have also failed and clinical programs have been suspended, in most cases when the route of administration was systemic, highlighting the existing challenges notably with respect to effective ASO delivery. In this review we summarize the recent advances and current status of antisense based-therapies for neuromuscular disorders, using successful as well as unsuccessful examples to highlight the variability of outcomes depending on the target tissue and route of administration. We describe the different ASO-mediated therapeutic approaches, including splice-switching applications, steric-blocking strategies and targeted gene knock-down mediated by ribonuclease H recruitment. In this over...Continue Reading

References

Jan 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·P C Zamecnik, M L Stephenson
Sep 1, 1986·Journal of Biochemical and Biophysical Methods·E Wickstrom
Feb 1, 1997·Annals of Neurology·M E CudkowiczR H Brown
Jun 1, 1997·Antisense & Nucleic Acid Drug Development·J Summerton, D Weller
Sep 15, 1997·Nucleic Acids Research·M GilarA S Cohen
Nov 6, 2004·Science·Aurélie GoyenvalleOlivier Danos
Aug 1, 2006·The Journal of Clinical Investigation·Richard A SmithDon W Cleveland
Nov 17, 2006·Biochemical and Biophysical Research Communications·Harleen KaurSouvik Maiti
Nov 17, 2007·The Journal of Clinical Investigation·Thurman M WheelerCharles A Thornton
Dec 28, 2007·The New England Journal of Medicine·Judith C van DeutekomGert-Jan B van Ommen
Jan 22, 2009·Human Mutation·Annemieke Aartsma-RusJohan T den Dunnen
Feb 5, 2009·Annals of Neurology·Jeffrey D Rothstein
Jul 18, 2009·Science·Thurman M WheelerCharles A Thornton
Apr 17, 2010·Neuromuscular Disorders : NMD·Virginia Arechavala-GomezaFrancesco Muntoni
Mar 25, 2011·The New England Journal of Medicine·Nathalie M GoemansJudith C van Deutekom
Sep 13, 2011·PloS One·Melvin M EversWilleke M C van Roon-Mom
Oct 6, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jeffrey B CarrollMichael R Hayden
Oct 13, 2011·Nature Reviews. Neurology·Peter M Andersen, Ammar Al-Chalabi
Mar 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Johanna E LeeThomas A Cooper
Aug 4, 2012·Nature·Thurman M WheelerCharles A Thornton
Sep 13, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Adeline VulinLuis Garcia
Jun 12, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Maëva Le HirStéphanie Lorain
Jul 24, 2013·Journal of Anatomy·Monir ShababiSabine S Rudnik-Schöneborn
Aug 3, 2013·Annals of Neurology·Jerry R MendellUNKNOWN Eteplirsen Study Group
Mar 25, 2014·Current Drug Targets·Tommaso IannittiBeniamino Palmieri
May 2, 2014·Neuromuscular Disorders : NMD·Jean K MahNathalie Jette
Oct 30, 2014·Nucleic Acid Therapeutics·Fritz Eckstein

❮ Previous
Next ❯

Citations

Jun 29, 2021·Médecine sciences : M/S·Amel Saoudi, Aurélie Goyenvalle

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.