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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)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Mutation; Seizures
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Zeitschrift Nature medicine
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503200-001
Förderungen Hertie Foundation
Gemeinntzige Hertie-Stiftung (Hertie Foundation)
DOI 10.1038/s41591-025-03656-0
WOS ID 001472566000001
Scopus ID 105003178388
PubMed ID 40263630
Erfassungsdatum 2025-05-10
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