Image: Mark Cunningham
Epilepsy affects 1pc of the world’s population and yet 30pc of patients don’t have a treatment that works. Prof Mark Cunningham wants to change this.
Epilepsy is a common neurological condition, which is characterised by repeated seizures, that affects more than 45,000 people in Ireland. It can develop at any age and rates are rising among the over 65s. The condition is the main focus of Prof Mark Cunningham’s research. He is Ellen Mayston Bates professor of neurophysiology of epilepsy at the School of Medicine in Trinity College Dublin.
Cunningham completed a BSc in physiology at Queen’s University Belfast and a PhD in physiology at the University of Bristol before taking up several postdoctoral and fellowship positions in institutions across the UK and in Germany. He started in his current role in 2018. He is a funded investigator at the FutureNeuro Science Foundation Ireland (SFI) Research Centre, where he has established, for the first time in Ireland, the capacity to conduct live human brain tissue studies from patients with refractory epilepsy. His work is supported by SFI and the UK Medical Research Council.
‘I was fascinated by how brain cells communicate with each other’
Tell us about your current research.
The primary focus of the laboratory is brain tumour-related epilepsy (BTRE). Epilepsy is one of the most common neurological conditions, affecting about 1pc of the world’s population. Currently, only 70pc of patients living with epilepsy have adequate control of the condition, meaning that 15-20m people must live with the crippling burden of drug-resistant seizures.
There are many causes of epilepsy (for example, genetics, brain injury/trauma, stroke or lack of oxygen to the brain) but a common cause in children and adults can be a brain tumour.
Seizures are a common symptom for patients with a brain tumour and are poorly controlled. These seizures are due to an increased level of a chemical messenger, or neurotransmitter, around the tumour. Neurotransmitters such as glutamate allow brain cells to talk to one another. Glutamate does this by exciting brain cells. However, excessive levels of glutamate overexcite brain cells around the tumour to cause seizures.
Glutamate also acts to promote the growth and movement of tumour cells into space previously occupied by brain cells that have been killed by high levels of glutamate. The tumour essentially hijacks the glutamate system for its own end – to promote seizures and its ability to spread.
Our current research aims to examine novel therapies that could be used to stop seizures in patients with BTRE. We are using two approaches in this regard. Firstly, we are examining novel pharmacological agents that act on a receptor that is activated by glutamate. Secondly, we are testing a gene therapy approach that will deliver a protein to the brain that, in the presence of excessive glutamate, will silence hyperexcitable brain cells to stop the seizures.
In your opinion, why is your research important?
BTRE has a significant impact on the quality of life of patients and the treatment of the condition is complicated by the fact that the patient has two significant simultaneous pathologies. On average, roughly 300 adults will present every year with primary brain cancer in Ireland. Seizures are the second most common presenting symptom of the tumour and will endure during the disease condition. Despite various care options (surgery, radiation, chemotherapy), seizures persist and novel precision-based treatments are urgently required.
What inspired you to become a researcher?
I was a curious child and would drive my parents demented by taking apart various items at home to try and understand how they worked!
My scientific journey began at secondary school at the Abbey Grammar CBS in Newry. My science teachers were inspirational and provided fantastic opportunities to participate in events such as the Young Scientist exhibition and British Science Association annual meetings. The school library also had a subscription to the New Scientist, and I enjoyed reading about the latest developments in science and health.
In terms of becoming a neuroscientist, I have a specific memory of learning about how brain cells communicate with each other using neurotransmitters – a process known as synaptic transmission. I was immediately fascinated by how this signalling process could underlie normal brain function and go wrong to produce neurological or psychiatric disease states.
What are some of the biggest challenges or misconceptions you face as a researcher in your field?
I think the challenge for any researcher at the minute is a balancing act between the increasing number of roles we now must excel at within a university environment. It means the job is multifaceted and never boring, but I have to fight hard to make time to still get in the lab and that’s the job I was trained for and enjoy doing!
Do you think public engagement with science has changed in recent years?
I think the public, in general, are motivated to understand science but are perhaps experiencing a degree of burnout from the media coverage of science during the recent pandemic. I hope the curiosity is still there, but I think as a community we must navigate alternative routes in terms of engagement.
From my own experience, I enjoy collaborating with the arts to develop cross-disciplinary approaches. I recently worked with Owen Boss, ANU Productions and the Royal Northern College of Music on a mixed-media installation called The Wernicke’s Area which was exhibited at IMMA. This work reflects the personal response of Debbie Boss, the wife of ANU’s co-artistic director and visual artist Owen Boss, to her brain tumour and associated seizures.
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