# Development and validation of a viral vector for targeted inhibition of DG granule cells

> **NIH NIH R21** · EMORY UNIVERSITY · 2023 · $234,750

## Abstract

PROJECT SUMMARY/ABSTRACT
Epilepsy is one of the most common neurological disorders. Approximately one third of patients are drug-
resistant, underscoring the need for alternative therapies. One of the biggest challenges to developing disease-
modifying therapies is the limited understanding of the underlying mechanisms behind the initiation and
propagation of seizures. We propose to develop a novel, translational gene therapy that targets dentate gyrus
(DG) granule cells, which have been shown to act as a seizure gate. We will make use of a promoter specific to
DG granule cells, Prospero-related homeobox 1 (Prox-1), to selectively express the inhibitory DREADD,
hM4D(Gi), in these cells. We hypothesize that this novel gene therapy with high translational potential will
effectively suppress spontaneously recurring seizures in the intrahippocampal kainic acid (IHKA) mouse model
of temporal lobe epilepsy. We will first develop and test the sensitivity and specificity of a truncated Prox-1
promoter and enhancers (Aim1). We then will examine the efficacy of a Prox-1::hM4D(Gi)-YFP viral vector in
inhibiting DG granule cells and suppressing chronic seizures in the IHKA mouse model of epilepsy, while also
testing memory effects (Aim 2). Development of an effective and highly translatable therapy can help us better
understand the mechanisms at play during seizures, as well as improve treatment in patients with drug-resistant
epilepsy. In addition to its utility in epilepsy, a Prox1-driven expression vector could have potential applications
in Alzheimer’s disease and neuropsychiatric disorders as well as in lymphatic and cancer research.

## Key facts

- **NIH application ID:** 10648833
- **Project number:** 1R21NS132071-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** ROBERT E GROSS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $234,750
- **Award type:** 1
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10648833

## Citation

> US National Institutes of Health, RePORTER application 10648833, Development and validation of a viral vector for targeted inhibition of DG granule cells (1R21NS132071-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10648833. Licensed CC0.

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