# Genetic Determinants of Epilepsy in Murine Systems

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $949,189

## Abstract

PROJECT SUMMARY
Developmental and Epileptic Encephalopathies (DEE) are individually rare but collectively substantial
neurodevelopmental disorders characterized by debilitating seizures and unremitting neurological comorbidities.
Dedicated exome sequencing efforts have led to unprecedented success in DEE gene discovery, with one-third
or more cases that are brought to the genetics clinic resulting in a clear genetic diagnosis. This new insight has,
in turn, created high expectations for precision or personalized medicine to deliver new therapies to families who
otherwise do not have many options for disease mitigation, since conventional drug therapy is ineffective for
most symptoms in any given DEE. In principle, gene therapy offers potential for treating any symptom caused
by a defective gene because it is based on replacing or eliminating it in situ. Among the barriers to clinical
application include the mode and the timing of delivery, particularly for neurodevelopmental disease, and the
concern about side effects from unintended impact on gene expression in cell types that do not require attention.
The purpose and the design of this renewal proposal is to address these barriers directly using ready manipulable
mouse models to examine key issues in the development and progression of DEE and the prospects for gene
therapy. First, we will apply new methods explicitly designed to detect epileptiform activity and developmental
milestones in mouse pups, representing an understudied but most appropriate age to model a childhood disease.
We will then use mouse genetics tools to drive gene expression in different neuron types or developmental ages
in these models, in order to determine the cellular etiology and critical window for disease development. Last,
we will extend RNA-based gene therapy efforts to these models, testing for both effective mitigation of pathogenic
features while monitoring accompanying changes in global gene expression. To accomplish these goals we have
assembled a team of four laboratories each contributing complementary expertise. Through this synergistic,
collaborative effort, we expect to make significant strides in understanding the basis of disease in three striking
models of DEE with the potential to advance new treatments in the clinic.

## Key facts

- **NIH application ID:** 10457441
- **Project number:** 5R01NS031348-31
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** WAYNE N. FRANKEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $949,189
- **Award type:** 5
- **Project period:** 1993-01-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457441

## Citation

> US National Institutes of Health, RePORTER application 10457441, Genetic Determinants of Epilepsy in Murine Systems (5R01NS031348-31). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10457441. Licensed CC0.

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