Abstract
There are few disease-modifying therapeutics for neurodegenerative diseases, but successes on the development of antisense oligonucleotide (ASO) therapeutics for spinal muscular atrophy and Duchenne muscular dystrophy predict a robust future for ASOs in medicine. Indeed, existing pipelines for the development of ASO therapies for spinocerebellar ataxias, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, Parkinson disease, and others, and increased focus by the pharmaceutical industry on ASO development, strengthen the outlook for using ASOs for neurodegenerative diseases. Perhaps the most significant advantage to ASO therapeutics over other small molecule approaches is that acquisition of the target sequence provides immediate knowledge of putative complementary oligonucleotide therapeutics. In this review, we describe the various types of ASOs, how they are used therapeutically, and the present efforts to develop new ASO therapies that will contribute to a forthcoming toolkit for treating multiple neurodegenerative diseases.
Glossary
- AD=
- Alzheimer disease;
- ALS=
- amyotrophic lateral sclerosis;
- ASO=
- antisense oligonucleotide;
- cET=
- constrained ethyl;
- DMD=
- Duchenne muscular dystrophy;
- ESE=
- exonic splicing enhancer;
- FAP=
- familial amyloid polyneuropathy;
- FDA=
- Food and Drug Administration;
- FTD=
- frontotemporal dementia;
- HD=
- Huntington disease;
- LNA=
- locked nucleic acid;
- MOE=
- methoxyethyl;
- OMe=
- O methyl;
- PD=
- Parkinson disease;
- PMO=
- phosphorodiamidate morpholino;
- PNA=
- peptide nucleic acid;
- PO=
- phosphodiester;
- PS=
- phosphorothioate;
- SCA=
- spinocerebellar ataxia;
- SMA=
- spinal muscular atrophy;
- SMN=
- survival motor neuron;
- SSO=
- splice-switching oligonucleotide;
- STAU1=
- Staufen1
Footnotes
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.
The Article Processing Charge was waived at the discretion of the Editor.
- Received December 17, 2018.
- Accepted in final form February 14, 2019.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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