Targeting AMPA receptors in brain tumour related epilepsy: A precision medicine approach

Nazia Rafiq

Brain Tumour-related Epilepsy (BTRE), is defined as symptomatic epileptic seizures secondary to gliomas. BTRE is debilitating and difficult to control and seizures are closely related to the recurrence/progress of the tumour. Seizures are the first presenting symptom in a large proportion of gliomas.

Increasing seizure burden and anti-seizure medication (ASM) use is associated with reduced cognitive performance, and dramatically reduced physical and mental health. Given the limited efficacy of current treatments for BTRE, there is an urgency to expedite novel therapies.

Around the tumour is an area of brain tissue called the peritumoural region. This region contains tumour cells that attempt to invade the surrounding normal brain tissue. These invading tumour cells hijack a neurotransmitter found in the brain, glutamate, to promote their movement and growth in the brain.

Tumour cells can also release glutamate so that the transmitter reaches very high levels around the tumour. Glutamate acts to produce hyper-excitability in the brain by a) activating a particular receptor, the AMPA receptor, and b) altering normal neuronal behaviour around the tumour. This activation of AMPA receptors leads to a reduction in the threshold required for seizures to occur and promote tumour growth.

Using human brain tumour cell lines, live mouse peritumoral brain tissue, and novel clinically relevant drugs, this project will assess the contribution of the AMPA receptors to seizure generation and, tumour growth. Overall, the information generated by the project will aim to improve treatment options for patients using drugs that target the AMPA receptor.