In an effort to make the lives of those living with epilepsy much easier, Dr Tobias Engel of RCSI is looking to develop a new drug treatment.
For more than 37,000 people in Ireland, living with epilepsy can be very challenging. It ranges in severity, but all affected experience traumatic seizures at some point in their life and in some cases regularly.
But, despite its prevalence, treatments and diagnostics have yet to reach a level that most medical practitioners would be happy with, which is why Dr Tobias Engel from the Royal College of Surgeons in Ireland (RCSI) is helping to not only create a proven medication for epilepsy, but also an easier and more accessible means to diagnose it.
After obtaining his undergraduate degree in molecular biology and biochemistry at the Autonomous University of Madrid in Spain, he went on to complete a PhD at the Molecular Biology Centre in Madrid, trying to identify new drug targets for Alzheimer’s disease.
In 2006, he made the move to RCSI to take up a postdoctoral position studying molecular pathomechanisms during epilepsy. Since 2014, has led his own research group to identify new diagnostics and therapeutics for epilepsy based on purinergic signalling.
He was recently awarded more than €500,000 by Science Foundation Ireland to further his research under the Career Development Awards.
What inspired you to become a researcher?
For as long as I can remember, there was only one thing I really wanted to do as an adult, which was to work as a researcher.
The reason for choosing neuroscience is probably related to a specific lecturer I had during my undergraduate studies teaching neuroscience. I remember this lecturer being particularly inspiring and he most certainly was the one who would have set off the spark that inspired me to pursue a career in neuroscience.
Can you tell us about the research you’re currently working on?
The main focus of my postdoctoral studies was to decipher the different molecular pathways activated in the brain following seizures.
One of these pathways involved the neurotransmitter system, otherwise known as the adenosine-5′-triphosphate (ATP) release in the brain, which I am currently working with.
The first experiments carried out in 2012 showed potent anticonvulsant properties of drugs interfering with this system and also led to my first independent research grant, the Starting Investigator Research Grant from SFI in 2014.
My research group, which started with one PhD student in 2014, kept on growing continuously and consists now of five PhD students, three postdocs and one research assistant.
Over the past few years, I have obtained funding from various funding agencies, including national and international agencies.
I am currently the coordinator of a European-wide consortium, with the main research focus on ATP signalling in different brain diseases.
Another focus of my research is the identification of novel diagnostics for seizures and prognostics for epilepsy development. This is also based on ATP signalling and involves the measurement of purine derivatives in the blood.
In your opinion, why is your research important?
Epilepsy is one of the most chronic brain diseases and affects more than 50m people worldwide, and the major challenges in epilepsy include drug resistance to current medication and a correct diagnosis.
Approximately 30pc of patients do not respond to drugs used in the clinic and, if effective, these drugs come along with severe side effects. These are merely symptomatic and not curing the underlying causes, leading to a lifelong dependency on medication.
A correct seizure/epilepsy diagnosis is in cases time-consuming, very costly and of limited availability. Consequently, the majority of epilepsy patients are treated on the basis of patient history and clinical features alone, leading to possible misdiagnosis or late treatment start.
What commercial applications do you foresee for your research?
We are currently developing a novel test for a cost-efficient seizure and epilepsy diagnosis.
This test will measure changes of a specific molecule in the blood. Blood concentration changes of this molecule will support the diagnosis of a seizure, and this test can be used in both hospitals and primary care.
What are some of the biggest challenges you face as a researcher in your field?
Epilepsy is a heterogeneous brain disease with multiple causes and pathological changes in the brain. Understanding what causes these changes and deciphering what molecules/proteins and pathways are involved still represents one of the major challenges to be resolved. This is probably not only true for epilepsy, but for most brain diseases.
Are there any common misconceptions about this area of research? How would you address them?
Probably the most common misconception in epilepsy is the notion that there is no need for novel diagnostics.
Currently, to diagnose epilepsy and thereby differentiate it from similar conditions, the patient must go to the hospital where their electroencephalogram (EEG) readings will be monitored continuously. However, not all hospitals have a monitored EEG room and there are long waiting lists for patients.
A second misconception is that there are sufficient drugs in the clinic to control seizures. Despite more than 25 drugs on prescription, more than 30pc of patients are drug-resistant and either have to undergo invasive surgery or keep experiencing ongoing seizures.
What are some of the areas of research you’d like to see tackled in the years ahead?
I think the development of novel diagnostics and therapeutics is the most urgent research field in epilepsy.
Novel, cheap and easy-to-handle diagnostics are needed to screen a large population. This would not only support epilepsy/seizure diagnosis, but also provide the patient with earlier and better treatment.
New therapeutics with effects in drug-refractory patients and with lasting, disease-modifying potential would not only reduce the number of patients not responding to treatment at all, but also spare patients from lifelong medication and its severe side effects.