Selective Potentiation of NaV1.1 Channels by Small Molecule XPC-837 in Dravet Mice Suppresses Spontaneous Seizures, Prevents SUDEP, and Increases Long Term Potentiation (S19.004)

Alison Cutts; Samuel Goodchild; Kristen Burford; Celine Dube; Samrat Thouta; Arjun Mahadevan; Matthew Waldbrook; Maegan Soriano; Maja Filipovic; Vishaal Rajani; Emily Hurley; Verner Lofstrand; Helen Clement; Davie Kim; Steve Wesolowski; James Empfield; JP Johnson

doi:10.1212/wnl.0000000000213153

June 9, 2026Neurology

Selective Potentiation of NaV1.1 Channels by Small Molecule XPC-837 in Dravet Mice Suppresses Spontaneous Seizures, Prevents SUDEP, and Increases Long Term Potentiation (S19.004)

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Key Points

The aim is to develop a small molecule that selectively enhances Nav1.1 channels to improve therapeutic outcomes in Dravet Syndrome.
Developed compound XPC-837 targeting Nav1.1 channels.
Conducted tests on Dravet mice models to evaluate seizure activity and potential therapeutic effects.
Assessed both spontaneous seizure frequency and prevention of sudden unexpected death in epilepsy (SUDEP).
XPC-837 significantly reduced spontaneous seizures compared to control groups.
The compound prevented SUDEP events observed in treated mice.
Long term potentiation was enhanced, suggesting improved neuronal function.

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Implication

Shows suppression of seizures in Dravet mice, indicating potential for improved treatments.

Abstract

To develop a novel, mechanistically differentiated, orally available compound with the potential to provide an improved therapeutic profile for the treatment of seizure and non-seizure symptoms of Dravet Syndrome (DS).

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Cite This Study

Cutts et al. (2026) studied this question.

synapsesocial.com/papers/6a2cf32afaef96ed7f055b56 https://doi.org/10.1212/wnl.0000000000213153

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Selective Potentiation of NaV1.1 Channels by Small Molecule XPC-837 in Dravet Mice Suppresses Spontaneous Seizures, Prevents SUDEP, and Increases Long Term Potentiation (S19.004)

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Selective Potentiation of NaV1.1 Channels by Small Molecule XPC-837 in Dravet Mice Suppresses Spontaneous Seizures, Prevents SUDEP, and Increases Long Term Potentiation (S19.004)

Key Points

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Implication

Abstract

Discussion

Cite This Study

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