# Mechanism and role of mTORC2 in seizure reduction

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $584,689

## Abstract

ABSTRACT
Epilepsy is a neurological disorder that poses a major threat to public health and is responsible for an enormous
economic and social burden. While some antiepileptic drugs have proven beneficial for the treatment of seizures,
they mainly provide symptomatic relief from seizures and often cause serious adverse effects. Thus, the
development of novel treatment strategies is of crucial importance. Here we focus on the mammalian target of
rapamycin (mTOR), which functions via two distinct complexes mTORC1 and mTORC2, and whose dysfunction
has been associated with epilepsy. Based largely on studies utilizing chronic treatment with the drug rapamycin,
it is currently believed that hyperactivation of mTORC1 leads to abnormal network rhythmicity associated with
epilepsy. However, chronic rapamycin treatment also inhibits the activity of mTORC2. Thus, it remains unclear
whether hyperactivation of mTORC1 or mTORC2 leads to the abnormal synchronized neuronal firing during
epilepsy. The goal of this new application is to define the mechanism by which activation of mTOR signaling
leads to epilepsy, with a special emphasis on mTORC2. In Aim 1, we will use molecular genetics to define the
role of mTOR complexes in seizures. In Aim 2, using phosphoproteomics, genetic, pharmacology and in utero
electroporation experiments, we will examine the mechanism by which inhibition of mTORC2 reduces seizures.
Finally, in Aim 3, we will use a novel selective and efficient inhibitor of mTORC2 and assess its broader
therapeutic potential for the suppression of seizures in different models of epilepsy.

## Key facts

- **NIH application ID:** 10747875
- **Project number:** 5R01NS124145-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** JEANNIE CHIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $584,689
- **Award type:** 5
- **Project period:** 2021-12-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747875

## Citation

> US National Institutes of Health, RePORTER application 10747875, Mechanism and role of mTORC2 in seizure reduction (5R01NS124145-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10747875. Licensed CC0.

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