Viral vector–mediated expression of NaV1.1, after seizure onset, reduces epilepsy in mice with Dravet syndrome

Saja Fadila, Bertrand Beucher, Iria González Dopeso-Reyes, Anat Mavashov, Marina Brusel, Karen Anderson, Caroline Ismeurt, Ethan M. Goldberg, Ana Ricobaraza, Ruben Hernandez-Alcoceba, Eric J. Kremer*, Moran Rubinstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Dravet syndrome (DS), an intractable childhood epileptic encephalopathy with a high fatality rate, is typically caused by loss-of-function mutations in one allele of SCN1A, which encodes NaV1.1, a 250-kDa voltage-gated sodium channel. In contrast to other epilepsies, pharmaceutical treatment for DS is limited. Here, we demonstrate that viral vector–mediated delivery of a codon-modified SCN1A open reading frame into the brain improves DS comorbidities in juvenile and adolescent DS mice (Scn1aA1783V/WT). Notably, bilateral vector injections into the hippocampus and/or the thalamus of DS mice increased survival, reduced the occurrence of epileptic spikes, provided protection from thermally induced seizures, corrected background electrocorticographic activity and behavioral deficits, and restored hippocampal inhibition. Together, our results provide a proof of concept for the potential of SCN1A delivery as a therapeutic approach for infants and adolescents with DS-associated comorbidities.

Original languageEnglish
Article numbere159316
JournalJournal of Clinical Investigation
Issue number12
StatePublished - 15 Jun 2023


FundersFunder number
American Dravet Syndrome Foundation
Spanish Dravet Syndrome Foundation
Yoran Institute for Human Genome Research
Direktoratet for UtviklingssamarbeidANR-19-CE37-0008
Agence Nationale de la RechercheANR-21-CE17-0056-01
Institut national de la santé et de la recherche médicale
Fondation pour la Recherche Médicale
Israel Science Foundation1454/17, 214/22
Tel Aviv University
Centre National de la Recherche Scientifique
Université de MontpellierANR-10-INBS-04


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