Gene Therapy for Polyglutamine Spinocerebellar Ataxias: Advances, Challenges, and Perspectives.
RNA interference
antisense oligonucleotides
gene editing
gene therapy
polyglutamine ataxias
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
02
09
2021
received:
20
04
2021
accepted:
06
09
2021
pubmed:
11
10
2021
medline:
17
3
2022
entrez:
10
10
2021
Statut:
ppublish
Résumé
Polyglutamine spinocerebellar ataxias (SCAs) comprise a heterogeneous group of six autosomal dominant ataxias caused by cytosine-adenine-guanine repeat expansions in the coding region of single genes. Currently, there is no curative or disease-slowing treatment for these disorders, but their monogenic inheritance has informed rationales for development of gene therapy strategies. In fact, RNA interference strategies have shown promising findings in cellular and/or animal models of SCA1, SCA3, SCA6, and SCA7. In addition, antisense oligonucleotide therapy has provided encouraging proofs of concept in models of SCA1, SCA2, SCA3, and SCA7, but they have not yet progressed to clinical trials. On the contrary, the gene editing strategies, such as the clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), have been introduced to a limited extent in these disorders. In this article, we review the available literature about gene therapy in polyglutamine SCAs and discuss the main technological and ethical challenges toward the prospect of their use in future clinical trials. Although antisense oligonucleotide therapies are further along the path to clinical phases, the recent failure of three clinical trials in Huntington's disease may delay their utilization for polyglutamine SCAs, but they offer lessons that could optimize the likelihood of success in potential future clinical studies. © 2021 International Parkinson and Movement Disorder Society.
Substances chimiques
Peptides
0
polyglutamine
26700-71-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2731-2744Informations de copyright
© 2021 International Parkinson and Movement Disorder Society.
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