The Mosaic Brain: towards a new understanding of focal epilepsies
Endeavour Project Grant
£174,998.26
Dr Amy McTague
Great Ormond Street Hospital NHS Foundation Trust
Epilepsy is the most common neurological condition affecting children and can significantly impact quality of life. At GOSH, around 150 children each year are treated for epilepsy linked to brain abnormalities, and genetic testing is used to identify DNA changes that may explain the condition. In some children, these changes are found only in the brain tissue causing seizures, known as genetic mosaicism, and may not be detectable in blood tests. We recently developed a test to detect these changes in brain tissue and now aim to adapt it for less invasive samples, enabling earlier diagnosis and improving detection using advanced sequencing techniques.
In this study, we will test the fluid surrounding the brain (cerebrospinal fluid, CSF) collected by a lumbar puncture (spinal tap). We will also test DNA fragments from electrodes that are inserted into the brain of some children as part of their assessment. We will improve our mosaic brain test with improved and deeper sequencing capabilities.
This project will improve understanding of the genetic changes that cause epilepsy and provide new insights into how and when seizures develop. Identifying these genetic changes could improve diagnosis, guide more personalised treatments, and support the development of targeted therapies. In the short term, improved brain tissue testing will be available within 12 months; in the medium term, new diagnostic tests could become part of clinical care within five years; and in the long term, discoveries of new genes and pathways may lead to tailored treatments within the next decade.
