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Wagner, M. ; Berecki, G.* ; Fazeli, W.* ; Nussbaum, C.* ; Flemmer, A.W.* ; Frizzo, S.* ; Heer, F.* ; Heinen, F.* ; Horton, R.* ; Jacotin, H.* ; Motel, W.* ; Spar, B.* ; Klein, C.* ; Siegel, C.* ; Hübener, C.* ; Stöcklein, S.* ; Paolini, M.* ; Staudt, M.* ; Tacke, M.* ; Wolff, M.* ; Petrou, S.* ; Souza, M.* ; Borggraefe, I.*

Antisense oligonucleotide treatment in a preterm infant with early-onset SCN2A developmental and epileptic encephalopathy.

Nat. Med., DOI: 10.1038/s41591-025-03656-0 (2025)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
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Early-onset SCN2A developmental and epileptic encephalopathy is caused by SCN2A gain-of-function variants. Here we describe the clinical experience with intrathecally administered elsunersen, a gapmer antisense oligonucleotide targeting SCN2A, in a female preterm infant with early-onset SCN2A developmental and epileptic encephalopathy, in an expanded access program. Before elsunersen treatement, the patient was in status epilepticus for 7 weeks with a seizure frequency of 20-25 per hour. Voltage-clamp experiments confirmed impaired channel inactivation and increased persistent current consistent with a gain-of-function mechanism. Elsunersen treatment demonstrated a favorable safety profile with no severe or serious adverse events reported after 19 intrathecal administrations over 20 months. After administration in combination with sodium channel blockers, status epilepticus was interrupted intermittently and ultimately ceased after continued dosing. A >60% reduction in seizure frequency corresponding to five to seven seizures per hour was observed, which has been sustained during follow-up until the age of 22 months. These data provide preliminary insights on the safety and efficacy of elsunersen in a preterm infant. Additional investigation on the benefits of elsunersen in clinical trials is warranted.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mutation; Seizures
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Grants Hertie Foundation
Gemeinntzige Hertie-Stiftung (Hertie Foundation)