# Network Pharmacology for Epilepsy Prevention

> **NIH NIH R43** · PREVEP, INC. · 2022 · $410,113

## Abstract

ABSTRACT
Prevention of epilepsy is a major unmet need in neurology. Approximately 20% of all epilepsy is
due to acute brain insult such as traumatic brain injury (TBI, 5%), stroke (10%), and CNS infection
(~5%).Following these injuries, there is a latency of days to years before epilepsy develops. This
offers opportunity to intervene with treatment to prevent or modify epilepsy. No such treatment
exists.
Epilepsy is a complex network phenomenon. Epileptogenesis after acute CNS injury involves
different pathophysiological processes. We have previously proposed that rational combinations
of drugs that engage different targets of the epileptogenic network may be a more effective
preventive treatment strategy than treatment with single specific drugs. We recently tested the
network approach in rodent models of epilepsy after status epilepticus (SE) by rationally
combining a variety of clinically approved drugs that target epileptogenesis by various
mechanisms, including anti-inflammatory, anti-oxidant, neuroprotective, and neurotransmitter-
modulating effects. Positive outcome from those studies provides the basis for the present
proposal to develop epilepsy prevention therapy based on network pharmacology and the
repurposing of FDA approved drugs.
We shall
(1) Compare pharmacokinetics, tolerability and efficacy of treatment with two drug combinations
of FDA approved drugs (PrevEp001 and PrevEp002) with good safety profile and different
antiepileptogenic effects (triple combinations) in prevention and/or amelioration of PTE in in a
validated TBI model of PTE, the rat fluid percussion model
(2) Develop novel i.v. formulation(s) of the triple combination and establish a GMP manufacturing
process to enable clinical trial supply.
(3) Evaluate tolerance and toxicity of the i.v. triple combination formulation treatment in rats by
conducting a GLP compliant multiple dose toxicity study.
(4) Conduct a pre-IND meeting with the FDA using data obtained from the present project and
from our previous SE epileptogenesis studies to allow human phase I-IIa development programs.
Overall, the project will provide the basis for conducting the first in human PoC study with the
triple combination.

## Key facts

- **NIH application ID:** 10490303
- **Project number:** 5R43NS119081-02
- **Recipient organization:** PREVEP, INC.
- **Principal Investigator:** Pavel Klein
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $410,113
- **Award type:** 5
- **Project period:** 2021-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490303

## Citation

> US National Institutes of Health, RePORTER application 10490303, Network Pharmacology for Epilepsy Prevention (5R43NS119081-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490303. Licensed CC0.

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