Growing up, one of Dr. David Henshall’s best friends suffered from epilepsy, but it was ultimately an academic interest that led him to the world of epilepsy research.
“I spent a semester in the final year of my undergrad pharmacology course learning how to do electrophysiological recordings in brain slices,” explains Dr. Henshall. “That got me hooked on neuroscience. Then when I was getting my PhD, a project focused on identifying neuroprotective drugs for stroke got me curious about cell death mechanisms. I was encouraged by my post-doc mentor to look into the apoptosis signaling pathways in epilepsy rather than stroke. Within a few months of starting my post-doc, I was in a hospital basement digging through patient seizure diaries, testing brain samples from patients who had surgery for drug-resistant epilepsy as well as learning how to model temporal lobe epilepsy in rats. I immediately liked the ability to study both human ‘living’ brain tissue and use animal models; it’s the approach I’ve taken ever since.”
“Epigenetic approaches hold promise for their ability to alter the on/off ‘switches’ that control gene expression. We’re starting to learn ways to do this in a directed manner.”
Dr. Henshall says that this interest is what drives him to work toward finding a cure for epilepsy in his research today.
“We have three main areas of study in my lab,” he explains. “The major focus is on molecules called microRNAs. These are made of RNA but are ‘non-coding.’ That means they don’t get translated into a protein but remain in the cell, working by sticking onto [protein-coding] messenger RNAs. About 10 years ago, it emerged that several had targets that affect the structure and function of synapses. We have been studying what these do and whether or not we can modify brain excitability by increasing or decreasing their levels. One in particular seems to have potent disease-modifying effects which we’re excited about. The same molecules are potential biomarkers of epilepsy so we have some projects that are measuring levels in body fluids such as blood and CSF to see if we can develop a test that might support diagnosis.
“The two other interests in my lab are neuroinflammation and autoimmune mechanisms of epilepsy. The autoimmune interests are a focus of current funding from CURE. We are collaborating with Angela Vincent and Sarosh Irani at Oxford University to understand how auto-antibodies against a little-understood synaptic protein called LGI1 leads to epilepsy. Such autoimmune epilepsies are increasingly discovered but the mechanisms are still poorly understood so this is an exciting area to be working on.”
Dr. Henshall also finds excitement and motivation in the challenges set before epilepsy researchers at this moment in history.
“An obvious grand challenge is to develop disease-modifying treatments for genetic as well as acquired epilepsies,” said Dr. Henshall. “This could mean precision therapeutics or gene editing techniques for the genetic epilepsies. And for acquired forms, it means it may be possible to use a ‘network’ drug approach – something that exerts effects across several pathways. Epigenetic approaches hold promise for their ability to alter the on/off ‘switches’ that control gene expression. We’re starting to learn ways to do this in a directed manner. There’s a lot of exciting research happening here.”
As his work with epilepsy research has progressed, Dr. Henshall has also created new opportunities to connect with those who are personally impacted by the disease.
“For a long time, I had almost no interaction with people with epilepsy,” he explains. “Now, things are different. I look for opportunities and try and get people in my lab to visit the EEG unit in the hospital and observe neurosurgeries. We also run ‘lay lecture’ nights at my institute co-organized by the main epilepsy patient group in Ireland. This creates opportunities to cover new research developments, new treatment and diagnoses, and gives families and their caretakers an opportunity to ask questions. It also connects those of us at the institute with the people we are working to help in a real and meaningful way. I hope we can do much more of this in the days ahead. I feel enormously privileged to do what I do. I’ve been inspired by many people who work in the field. I hope that my research can make a useful contribution.”