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Current Status of Antisense Oligonucleotide-Based Therapy in Neuromuscular Disorders

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A Correction to this article was published on 04 August 2020

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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 overview, we discuss the merits and challenges of the current ASO technology, and discuss the future of ASO development.

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Change history

  • 04 August 2020

    The second author, which currently reads as: Adeline Vulin-Chaffiol.

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Authors and Affiliations

  1. Université Paris-Saclay, UVSQ, Inserm, END-ICAP, 78000, Versailles, France

    Flavien Bizot, Adeline Vulin & Aurélie Goyenvalle

  2. SQY Therapeutics, Université de Versailles St-Quentin, Montigny le Bretonneux, France

    Adeline Vulin

  3. LIA BAHN, Centre scientifique de Monaco, Monaco, Monaco

    Aurélie Goyenvalle

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  1. Flavien Bizot
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  2. Adeline Vulin
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  3. Aurélie Goyenvalle
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Correspondence to Aurélie Goyenvalle.

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AV is an employee of SQY therapeutics, developing tcDNA-ASOs. AG and FB declare no conflict of interest.

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Authors are supported by the Institut National de la santé et la recherche médicale (INSERM), the Association Monegasque contre les myopathies (AMM), the Duchenne Parent project France (DPPF) and the Fondation UVSQ. AV is an employee of SQY therapeutics.

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Bizot, F., Vulin, A. & Goyenvalle, A. Current Status of Antisense Oligonucleotide-Based Therapy in Neuromuscular Disorders. Drugs 80, 1397–1415 (2020). https://doi.org/10.1007/s40265-020-01363-3

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