Haploinsufficiency, Dominant Negative, and Gain-of-Function Mechanisms in Epilepsy: Matching Therapeutic Approach to the Pathophysiology.
Antisense oligonucleotides
Epilepsy
Gene therapy
Genetics
Precision therapies
Journal
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
ISSN: 1878-7479
Titre abrégé: Neurotherapeutics
Pays: United States
ID NLM: 101290381
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
accepted:
30
09
2021
pubmed:
15
10
2021
medline:
4
3
2022
entrez:
14
10
2021
Statut:
ppublish
Résumé
This review summarizes the pathogenic mechanisms that underpin the monogenic epilepsies and discusses the potential of novel precision therapeutics to treat these disorders. Pathogenic mechanisms of epilepsy include recessive (null alleles), haploinsufficiency, imprinting, gain-of-function, and dominant negative effects. Understanding which pathogenic mechanism(s) that underlie each genetic epilepsy is pivotal to design precision therapies that are most likely to be beneficial for the patient. Novel therapeutics discussed include gene therapy, gene editing, antisense oligonucleotides, and protein replacement. Discussions are illustrated and reinforced with examples from the literature.
Identifiants
pubmed: 34648141
doi: 10.1007/s13311-021-01137-z
pii: 10.1007/s13311-021-01137-z
pmc: PMC8608973
doi:
Substances chimiques
Oligonucleotides, Antisense
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1500-1514Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM119550
Pays : United States
Informations de copyright
© 2021. The American Society for Experimental NeuroTherapeutics, Inc.
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