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Research Portfolio

GRANT TITLE:

Reprogramming of reactive glia into fast-spiking interneurons in a mouse model of Mesial Temporal Lobe Epilepsy

GRANT TYPE:

EMERGING LEADER FELLOWSHIP AWARD

grant amount:

£299.862.56

lead investigator:

Dr Nicolas Marichal Negrin

Co-Investigators:

-Professor Benedikt Berninger

institution:

King’s College London

Background

Temporal Lobe epilepsy is one of the most common forms of epilepsy. In temporal lobe epilepsy, a structure in the brain called the hippocampus is damaged, meaning that some nerve cells are lost, and support cells (called glia) are changed. This makes the cells in the brain more excitable, contributing to seizures.

Some of the nerve cells that are lost in temporal lobe epilepsy are called ‘interneurons’. Interneurons help to regulate electrical activity in the brain by inhibiting nerve cells. This loss of interneurons is therefore likely to be contributing to seizures.

"This project will further advance a novel cell-based therapeutic strategy to stop seizures in a common form of focal epilepsy, providing solid grounds for expanding its application to other forms of epilepsy.

The Study

The team at King’s College London have been converting glial cells in the brain into interneurons in a mouse model of temporal lobe epilepsy.

Building on these promising results, this project aims to improve the conversion of glia into interneurons using a new ‘recipe’. The team will try to create the exact kind of cells that have been lost in temporal lobe epilepsy and see how effective the new cells are at restoring the balance of electrical activity in the brain.

Significance

For many people with temporal lobe epilepsy, current antiseizure medications don’t work, meaning we desperately need innovative new treatments. This research will advance this cell-reprogramming technique and explore if replacing the lost interneurons could be a potential future treatment for temporal lobe epilepsy. The team hope that this technology could be tested in clinical trials and become a treatment for epilepsy.