# Defining novel mechanisms of sudden death in Dravet syndrome: Dysregulation of sodium channels in the heart

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $424,758

## Abstract

Project Summary
Sudden, unexpected death in epilepsy (SUDEP) is a fatal complication, occurring in patients with epilepsy, who
were otherwise healthy. Dravet syndrome (DS), which results from a loss of function of the sodium channel (NaV)
isoform NaV1.1, is associated with a particularly high risk of SUDEP. Notably, the unexpected mortality of SUDEP
mirrors cases of sudden cardiac death (SCD) – unexpected death resulting from cardiac arrhythmias. Emerging
evidence points to physiological commonalities between the brain and the heart, suggesting that the very
molecular mechanisms that underlie epileptic disorders could also directly impact the heart, leading to life-
threatening cardiac arrhythmias and thereby, SCD. However, the precise mechanisms by which DS directly
impact the heart to promote cardiac arrhythmias and SCD remain unknown. Thus, we propose to utilize models
of DS to address this gap in knowledge and to explore the role of direct cardiac remodeling in SCD. Using these
models, we will test the hypothesis that defects in NaVs that underlie inherited epileptic disorders, such as Dravet
syndrome, dysregulate cardiac Na+/Ca2+ cycling, thereby promoting life-threatening arrhythmias and contributing
to SCD. Thus, we propose to: 1) Define the phenotypic and structural impacts of tissue-specific expression of
DS-associated defects. 2) Determine the functional impact of DS-associated Na+/Ca2+ signaling nanodomain
remodeling on cardiac Ca2+ handling. 3) Assess efficacy of targeting Na+/Ca2+ signaling nanodomains for SCD
prevention. Information gleaned from these studies will be used to develop new therapeutic approaches to treat
SCD in DS.

## Key facts

- **NIH application ID:** 10366777
- **Project number:** 1R01NS121234-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Przemyslaw Radwanski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $424,758
- **Award type:** 1
- **Project period:** 2021-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10366777

## Citation

> US National Institutes of Health, RePORTER application 10366777, Defining novel mechanisms of sudden death in Dravet syndrome: Dysregulation of sodium channels in the heart (1R01NS121234-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10366777. Licensed CC0.

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