# Gluconeogenic control of Dravet Syndrome

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $504,392

## Abstract

Although altered metabolism is rapidly emerging as a key feature of epilepsies, it has not been
systematically investigated in any genetic form of pediatric epilepsy. Dravet syndrome (DS), a
catastrophic childhood epilepsy associated with de novo mutations in a voltage-activated sodium
channel, Nav1.1 is one of the most common genetic epilepsies. DS patients suffer with intractable
early-life seizures, and debilitating comorbidities. Energy metabolism in comorbidities associated
with DS remain virtually unexplored. To address this unmet need, recent collaborative research
in our two laboratories revealed decreased glycolytic and oxygen consumption rates in a validated
zebrafish model of DS i.e., scn1Lab mutants. This was accompanied by downregulation of key
enzymes, pck1 and pck2, in the gluconeogenesis pathway. Here, we hypothesize that energy
disruption occurs in DS due to glucose dysregulation resulting in seizures and/or comorbidities.
The following aims are proposed to test this hypothesis. Aim 1 will determine if pharmacological
inhibition of pck1 and/or pck2 phenocopies metabolic and behavioral deficits in wildtype zebrafish.
Aim 2 will determine if pharmacological manipulation of pck1 and/or pck2 is therapeutic in
scn1Lab mutant zebrafish. These studies promise to provide a mechanistic explanation of the
metabolic defects observed in DS and could suggest novel avenues for therapeutic intervention.

## Key facts

- **NIH application ID:** 9990441
- **Project number:** 1R01HD102071-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Scott C Baraban
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,392
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990441

## Citation

> US National Institutes of Health, RePORTER application 9990441, Gluconeogenic control of Dravet Syndrome (1R01HD102071-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9990441. Licensed CC0.

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