2026 American Academy of Neurology Abstract Website

Silvana Frizzo¹, Matias Wagner², Malin Zaddach³, Claudia Nussbaum⁴, Geza Berecki⁵, Andreas Flemmer⁴, Florian Heinen⁶, Brian Spar¹, Martin Staudt⁷, Moritz Tacke³, Markus Wolff⁸, Walid Fazeli⁹, Steven Petrou¹, Marcio Souza¹, Ingo Borggraefe³
¹Praxis Precision Medicines, ²Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics and Comprehensive Epilepsy Center, Ludwig Maxmilians University Hospital; Institute of Human Genetics, Technical University of Munich; Institute for Neurogenomics, Helmholtz Centre Munich, German Research Center for Health and Environment (GmbH), ³Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics and Comprehensive Epilepsy Center, Ludwig Maxmilians University Hospital, ⁴Division of Neonatology, Dr. von Hauner Children’s Hospital, Ludwig Maximilians University Hospital, ⁵Ion Channels and Human Diseases Group, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, ⁶Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics and Comprehensive Epilepsy Center, ⁷Department of Pediatric Palliative Care, Ludwig Maximilians University Hospital, ⁸Swiss Epilepsy Center, Klinik Lengg AG, ⁹Department of Pediatric Neurology, Children’s Hospital, University Hospital Bonn

Objective:

This is a case report of the first complementary emergency use of the antisense oligonucleotide (ASO), elsunersen, and the precision sodium channel modulator, relutrigine, in an infant with severe early onset SCN2A developmental and epileptic encephalopathy (SCN2A-DEE) and refractory status epilepticus (SE).

Background:

Early onset SCN2A-DEE is a rare, fatal disorder characterized by developmental delay or regression, frequent, treatment-resistant seizures, typically beginning within days of birth. Clinical studies with a gapmer SCN2A ASO show significant seizure reduction, amongst other benefits. However, persistent network hyperexcitability in a developmentally altered brain may remain. Adjunctive precision sodium channel modulation could further stabilize excitability and enhance clinical outcomes. Elsunersen, an intrathecally-administered ASO in development for early onset SCN2A-DEE, has shown well-tolerated, significant, sustained seizure reduction. Relutrigine, a sodium channel functional state modulator, has demonstrated robust, sustained seizure reduction in a diverse DEE population.

Design/Methods:

A preterm infant (29+4 weeks gestation; birthweight 1400g) diagnosed prenatally with a pathogenic SCN2A variant presented with life-threatening SE and only partial effect of high-dose sodium channel blockers (SCBs). Following confirmation of gain-of-function status, elsunersen was initiated at 7 weeks, with 26 monthly doses administered to date (182.5mg total). Relutrigine was introduced two years later (0.5mg/kg daily) with the objective of enhancing clinical outcomes.

Results:

Elsunersen in combination with best standard-of-care ASMs (mainly SCBs) was well-tolerated. Early dosing led to SE cessation and revealed a temporal association with seizure reduction. Seizure frequency remained stable, maintained after tapering phenytoin at 14 months, with no further neurodevelopmental worsening. As early as three weeks after relutrigine commencement, parents and nursing staff reported moderate-to-significant improvement including fewer, less severe seizures, with no new safety findings. Continued improvement in clinical status permitted a previously unattainable reduction in carbamazepine dosage.

Conclusions:

First-in-patient findings point to elsunersen’s potential for enhancement via adjunctive precision sodium channel modulation addressing residual network hyperexcitability.