Engineered gene therapy to reduce seizures and restore balance in brain tumour-related epilepsy.
Explore Pilot Study
£38,502.60
Dr Kate Hills
University College London
Many people with epilepsy do not respond well to current medicines, and those who do often experience side effects such as tiredness, memory problems, and slowed thinking. This is especially true for people with brain tumours such as glioblastoma, where seizures are very common and often difficult to control. Normally, support cells in the brain called astrocytes help prevent seizures by removing excess glutamate, a chemical messenger that excites brain cells. They do this using a protein called glutamate transporter 1 (GLT-1). In glioblastoma, this protective system breaks down: GLT-1 is reduced and removed from the cell surface, while tumour cells release extra glutamate. As a result, brain networks become over-excitable and prone to seizures, which are now recognised as part of the disease itself rather than just a symptom.
The study will be carried out in a series of connected steps, moving from laboratory experiments to early testing in a mouse model of brain tumour-related epilepsy. First, I will design and build several modified versions of the GLT-1 protein, along with comparison versions. These will be tested in human cells to see how well they remove excess glutamate and how stable they are under conditions that normally cause GLT-1 to be lost from the cell surface. This step will allow identification of the strongest and most reliable version.
This work will provide early proof-of-concept that targeting astrocytes and glutamate clearance is a realistic, disease-focused way to treat epilepsy associated with brain tumours, helping guide future research and therapy development.
