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Current Geriatrics Reports

Published in:

08-01-2021 | Amyotrophic Lateral Sclerosis | Neurology of Aging (K Marder, Section Editor)

Antisense Oligonucleotide Therapeutics for Neurodegenerative Disorders

Author: Claudia M. Testa

Published in: Current Geriatrics Reports | Issue 3/2022

Abstract

Purpose of Review

Expanding therapeutic targets from proteins to RNAs opens up new possibilities for neurodegenerative disorders therapeutics development. Recently, a disease-modifying antisense oligonucleotide (ASO) agent was approved for spinal muscular atrophy, suggesting ASOs will fulfill their early promise and become a significant new therapeutic category for neurodegenerative disorders.

Recent Findings

ASOs are in human subjects testing for Huntington disease, monogenic forms of amyotrophic lateral sclerosis, Alzheimer disease, myotonic dystrophy, Leber congenital amaurosis, Usher syndrome, and retinitis pigmentosum, with many more in preclinical development. Current ASO strategies encompass RNA processing modulation, and RNA target breakdown. Broad ASO mechanism categories are protein restoring versus protein lowering. Individual ASO mechanisms of action range from mutation-specific to impacting many proteins.

Summary

Current ASOs show great promise in neurodegenerative disorders. Specific ASO designs and mechanisms may be more tenable in this disease area. Preclinical development is already leveraging early knowledge from these initial clinical trials to develop novel ASO cocktails, new ASO chemical modifications, and new ASO RNA and protein targets.

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Title: Antisense Oligonucleotide Therapeutics for Neurodegenerative Disorders
Author: Claudia M. Testa
Publication date: 08-01-2021
Publisher: Springer US
Keywords: Amyotrophic Lateral Sclerosis
Myotonic Dystrophy
Spinal Muscular Atrophy
Myotonic Dystrophy
Huntington's Disease
Published in: Current Geriatrics Reports / Issue 3/2022
Electronic ISSN: 2196-7865
DOI: https://doi.org/10.1007/s13670-020-00341-7

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