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Research Portfolio

GRANT TITLE:

Identification of brain cell mutations in focal epilepsy

GRANT TYPE:

EXPLORE PILOT STUDY

grant amount:

£29,988 over 24 months, awarded in 2023

lead investigator:

Professor Maria Thom

Co-Investigators:

- Professor Sanjay Sisodiya (UCL)
- Professor Sebastian Brandner (UCL)

institution:

University College London

Background

A third of patients with focal epilepsy (epilepsy starting from a specific brain region) do not respond to conventional antiseizure medications. While neurosurgical treatments have been increasingly used in a selected number of patients, achieving seizure freedom for about two-thirds, it is unknown why some patients do not respond to surgery. Furthermore, many patients being investigated for surgery will have depth-electrode studies to define the abnormal brain region; but, following this, a decision is sometimes made not to proceed with surgery and their seizures continue.

There is increasing recognition that gene mutations, present only in groups of brain cells in a localised brain region, are directly related to the epilepsy. Identifying these genes and their effects on the cells is important in diagnosis, identifying new treatment targets (with some already in clinical trials), as well as delineating the abnormal brain region for patients who do go on to surgical removal.

"We aim to establish a methodology to analyse ultra-small cell samples attached to brain electrodes that could facilitate personalised and novel epilepsy treatments. This would provide an opportunity for genetic characterization prior to surgical resective procedures and may enable diagnosis and indicate alternative treatments in patients who do not go on to have surgical treatment.

The Study

We propose in this pilot study to develop novel ways of extracting DNA from the few brain cells adherent to the removed electrodes, as well as from tissue samples. The DNA will be sequenced to identify the relevant genes causing the epilepsy. We aim to demonstrate this is achievable in a pilot group of epilepsy surgical candidates over two years.

Significance

This data has the potential to influence both the medical and surgical management of patients with focal epilepsy. We envisage that this service could be opened up to other UK centres, thus benefiting a larger population in whom epilepsy surgery is being considered or planned.

This study will also enable us to examine the relationship between the proportion of brain cells with mutations and electrical characteristics at the electrode site. Such information could enable more accurate planning of surgical resections following electrode studies, which may lead to optimal outcomes.