Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy.
Schneider MF, Vogt M, Scheuermann J, Müller V, Fischer-Hentrich AH, Kremer T, Lugert S, Metzger F, Kudernatsch M, Kluger G, Hartlieb T, Noachtar S, Vollmar C, Kunz M, Tonn JC, Coras R, Blümcke I, Pace C, Heinen F, Klein C, Potschka H, Borggraefe I (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 15
Journal Issue: 1
Abstract
OBJECTIVE: Heterozygous mutations within the voltage-gated sodium channel α subunit (SCN1A) are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of SCN1A are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches. METHODS: We investigated SCN1A mRNA expression and expression of two SCN1A related antisense RNAs in brain tissues in different age groups of pediatric non-Dravet patients who underwent surgery for drug resistant epilepsy. The effect of different antisense oligonucleotides (ASOs) directed against SCN1A specific antisense RNAs on SCN1A expression was tested. RESULTS: The SCN1A related antisense RNAs SCN1A-dsAS (downstream antisense, RefSeq identifier: NR_110598) and SCN1A-usAS (upstream AS, SCN1A-AS, RefSeq identifier: NR_110260) were widely expressed in the brain of pediatric patients. Expression patterns revealed a negative correlation of SCN1A-dsAS and a positive correlation of lncRNA SCN1A-usAS with SCN1A mRNA expression. Transfection of SK-N-AS cells with an ASO targeted against SCN1A-dsAS was associated with a significant enhancement of SCN1A mRNA expression and reduction in SCN1A-dsAS transcripts. CONCLUSION: These findings support the role of SCN1A-dsAS in the suppression of SCN1A mRNA generation. Considering the haploinsufficiency in genetic SCN1A related DS, SCN1A-dsAS is an interesting target candidate for the development of ASOs (AntagoNATs) based precision medicine therapeutic approaches aiming to enhance SCN1A expression in DS.
Authors with CRIS profile
Involved external institutions
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
ISAR Bioscience GmbH
Germany (DE)
F. Hoffmann-La Roche Ltd
Switzerland (CH)
Versameb AG
Switzerland (CH)
Schön Kliniken
Germany (DE)
Paracelsus Medizinische Privatuniversität
Austria (AT)
Klinikum der Universität München
Germany (DE)
Germany (DE)
ISAR Bioscience GmbH
Germany (DE)
F. Hoffmann-La Roche Ltd
Switzerland (CH)
Versameb AG
Switzerland (CH)
Schön Kliniken
Germany (DE)
Paracelsus Medizinische Privatuniversität
Austria (AT)
Klinikum der Universität München
Germany (DE)
How to cite
APA:
Schneider, M.F., Vogt, M., Scheuermann, J., Müller, V., Fischer-Hentrich, A.H., Kremer, T.,... Borggraefe, I. (2024). Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy. Translational Neuroscience, 15(1). https://doi.org/10.1515/tnsci-2022-0330
MLA:
Schneider, Marius Frederik, et al. "Brain expression profiles of two SCN1A antisense RNAs in children and adolescents with epilepsy." Translational Neuroscience 15.1 (2024).
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