Search
Close this search box.
Search
Close this search box.

Research Portfolio

GRANT TITLE:

Do babies with genetic epilepsy have more excitable neurons?

GRANT TYPE:

ENDEAVOUR PROJECT GRANT

grant amount:

£163,443 over 24 months, awarded in 2023

lead investigator:

Dr Amy McTague

Co-Investigators:

- Dr Jenny Lange (UCL)

institution:

UCL Great Ormond Street Institute of Child Health

Background

Many babies that present with genetic epilepsies have seizures that do not respond well to currently available treatments, and there is a lack of knowledge of how genetic changes lead to epilepsy in babies. Better understanding would enable researchers to design better, more effective treatments.

Some babies with epilepsy may have abnormal chloride levels in nerve cells, which affects the ability of GABA, a chemical in the brain, to calm excitable neurons down. This process may be happening in other types of epilepsy and in status epilepticus – where a seizure last longer than 6 minutes.  Identifying the cause of brain excitability in these epilepsies would facilitate the discovery of more versatile, targeted treatments.

"Epilepsy starting in the first year of life can be difficult to treat and has a huge impact for children and for their families. We now know that it is frequently caused by genetic abnormalities, often affecting ion channels and transporters. However the disease mechanisms for these and many other genetic epilepsies remain unclear. Using a patient-derived neuronal model, we will assess the impact of different genetic epilepsies on chloride balance in neurons, creating a high throughput system which will be amenable to novel therapy testing.

The Study

This research involves creating a lab model that closely mimics the impact of epilepsy on patients’ brains. People with epilepsy and those without (providing a baseline for normal cell activity etc.), who consented to take part in this research, have donated skin samples that will be transformed by the researchers into brain cells. These “brain cells in a dish” are a window into understanding the effects of the genetic changes that lead to epilepsy, including the ability to check chloride levels and electrical activity, as well as identify shared disease processes between the epilepsiesIn the future, tests will also be designed to assess various medications in the neurons at once to find treatments that act specifically on chloride levels and may be more targeted to the disease process than current treatments.

Significance

This project will lead to new understandings about why seizures occur, particularly in early life epilepsies, and potentially identify targeted new treatments. This would have a significant impact, as babies with this type of epilepsy have seizures that do not respond well to currently available treatments.