Much of your research focuses on microRNAs – what are they and how they might help people with epilepsy?
MicroRNAs are tiny gene regulators that help cells function properly. While most people think of genes as instruction manuals for making proteins – like SCN1A in Dravet syndrome, which forms electrical signal pores on nerve cells – microRNAs operate in the background, quietly adjusting how much protein gets made. They act between gene activation and protein production by binding to messenger RNA (mRNA) and preventing it from reaching the ribosome, where proteins are assembled. Imagine threading a shoelace through a boot – microRNAs are the knot that stops it.
In this way, microRNAs act as a gentle braking system, helping to prevent too much protein from being made. They also allow cells to fine-tune protein production, creating more complexity from the same genetic instructions.
What do you find most exciting about this approach to therapy?
What excites me most is how microRNAs can regulate dozens of mRNAs at once. In epilepsy, there usually isn’t just one faulty gene – hundreds may show altered activity. Targeting a single microRNA allows us to potentially reset multiple pathways at the same time.
The good news is we can design drug-like molecules that precisely target microRNAs, thanks to our understanding of their exact chemical makeup. By making subtle, targeted changes to gene activity, we hope to achieve longer-lasting seizure control. Because this approach works with our cells’ own system for regulating gene activity, it offers a safe and natural way to intervene.
How close are we to testing these therapies in people with epilepsy?
We’re already testing microRNA therapies in people. A clinical trial is underway for temporal lobe epilepsy, a drug-resistant form common in adults that’s not usually linked to an underlying genetic condition. That trial uses a virus to deliver an artificial microRNA directly to the part of the brain where seizures start. We’re working with a biotech company on a different strategy using antisense oligonucleotides (ASOs) – short DNA pieces that bind to and block microRNAs. ASOs don’t require viral delivery and can be reversed. One ASO we helped develop blocks an over-active microRNA found in temporal lobe epilepsy patients, and we’re hopeful it will enter clinical trials soon.
You’ve recently been involved in the development of a film on climate change and how this may affect people with epilepsy – can you tell us a bit more about this?
Two things came together. I’m the director of a national brain research centre in Ireland called FutureNeuro, which has a very active public engagement programme. I’m also involved in a commission set up by the International League Against Epilepsy (ILAE) to explore the impact of climate change on brain health.
Climate stressors like extreme heat, poor air quality, sleep disruption, and anxiety – frequent during heatwaves, wildfires, or displacement – can lower seizure thresholds and increase seizure frequency. People from lower-income backgrounds, racial and ethnic minorities, and those living in poorly insulated homes or under-resourced rural areas often face greater exposure to these risks and have fewer resources to adapt. One of the commission’s goals is to raise awareness of these challenges and push for more research in this area.
To raise awareness, we’ve produced a short film calling for brain health to be part of the climate conversation. The film urges better emergency planning and inclusive access to care. It also encourages researchers to reduce their carbon footprint. We hope it sparks dialogue between patients, scientists, policymakers, and the public about how to protect brain health in a changing world.
Looking ahead, what are your biggest hopes for the future of epilepsy research?
The past couple of decades have brought incredible advances in our understanding of which genes can cause epilepsy. We can even identify which genes are active in individual human brain cells now. Our ability to record and even modify brain activity is also improving rapidly. I expect we will see gene therapies for some rare epilepsies very soon. This will be a total game-changer for patients, families, and clinicians.
However, we are not just our genes. We must remember that life – and the brain – operates on a much larger scale: through cells, networks, and their connections to other organs and systems in the body. We won’t solve most epilepsies (or co-morbid conditions like depression and anxiety) by focusing on single genes alone.
Much more basic science is needed, along with flexible thinking and scientific strategies that bring together different disciplines. We need better communication between scientists studying other brain diseases and more sharing of new ways to model and study brain function. That said, I am excited and optimistic about where we will be by the time I retire!
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