RNA technologies for neurodegenerative diseases

Advantages and challenges

RNA interference (RNAi) technologies are being developed as potential gene therapies for a range of neurodegenerative diseases. These include:

Small interfering RNA

siRNA approaches have now begun to be developed for treatment of central nervous system (CNS) disorders including DNM2 related SPG, Alzheimer’s disease (AD), Parkinson’s disease (PD), and spinocerebellar ataxias.

Antisense Oligonucleotides

ASOs have been approved for neurological diseases including nusinersen for Spinal Muscular Atrophy (SMA) (developed by Ionis Pharmaceuticals and Biogen; approved in 2016).


All RNA-targeting and gene replacement therapies for neurological disorders face the issue of delivering sufficient levels of the drug product to specific target cell populations in the brain and spinal cord.

Challenges for RNAi therapeutics

The transient nature of RNA poses a challenge for disorders that would require repeated dosing.


Advances in genome sequencing have greatly facilitated the identification of genomic variants underlying rare neurodevelopmental and neurodegenerative disorders. Understanding the fundamental causes of rare monogenic disorders has made gene therapy a possible treatment approach for these conditions.

RNA interference (RNAi) technologies such as small interfering RNA (siRNA) microRNA (miRNA) short hairpin RNA (shRNA) and other oligonucleotide-based modalities such as antisense oligonucleotides (ASOs) are being developed as potential therapeutic approaches for manipulating expression of the genes that cause a variety of neurological diseases.

Here, we offer a brief review of the mechanism of action of these RNAi approaches; provide deeper discussion of the advantages, challenges, and specific considerations related to the development of RNAi therapeutics for neurological disease; and highlight examples of rare neurological diseases for which RNAi therapeutics hold great promise.

SOURCE:  Mol Aspects Med. 2022 Oct 15;101148. doi: 10.1016/j.mam.2022.101148. Online ahead of print. PMID: 36257857 Copyright © 2022. Published by Elsevier Ltd.

RNA interference (RNAi)-based therapeutics for treatment of rare neurologic diseases

Noelle D Germain  1 Wendy K Chung  2 Patrick D Sarmiere  3

1. Ovid Therapeutics, Inc., 1460 Broadway, New York, NY, 10036, USA.

2. Departments of Pediatrics and Medicine, Columbia University, 1150 St. Nicholas Avenue, Room 620, New York, NY, 10032, USA.

3. Ovid Therapeutics, Inc., 1460 Broadway, New York, NY, 10036, USA.

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