In a nutshell, tell us about your research?
My research focuses on early-onset genetic epilepsies. These forms of epilepsy can be devastating for patients and their families. It is not clear how the faulty genes cause epilepsy, but the problems are likely to start before birth, making them extremely challenging to study. I have established a way to develop human brain tissue in a laboratory environment, enabling me to alter genes of interest and study the consequences on the developing brain. I use this clinically applicable method to investigate disease mechanisms in genetic epilepsy (to find out how faulty genes or gene mutations can cause epilepsy) and as a screening platform for anti-seizure medications (ASMs).
What impact do you hope your research will have?
I hope to clearly establish the disease-causing mechanisms behind multiple forms of early-onset epilepsies. Around 24% of paediatric epilepsies diagnosed are caused by single genes, with many hard to control with ASMs and associated with developmental delay. A lot of these genes affect similar mechanisms in the brain. Identifying how much they overlap would help clinicians classify these patients better and improve identification of cases for clinical trials. The impact of ASMs on the developing human brain is also not well understood. Testing new or existing drugs in my clinical platform will provide critical information for determining which pose the least neurodevelopmental threat to unborn children.
What is the most interesting finding to come out of your project so far?
I used the developing human brain tissue platform to investigate a gene called STXBP1, one of the most common single-gene epilepsies. I recently published a paper demonstrating that STXBP1 is crucial for maintaining reliable communication between individual brain cells (also called synaptic signalling). However, to fully understand how the entire brain functions, it is essential to look at multiple brain cells collectively. My recent data suggests that faulty STXBP1 reduces the amount of brain activity present between large networks of brain cells and alters the expression of other genes important for synaptic signalling. This work will extend our understanding of how STXBP1 mutations cause early-onset epilepsy.
Why did you want to become Early Career Lead of the Institute’s Reproduction and Hormones Theme?
This week we’ve seen the publication of The Hughes Report, outlining redress recommendations for those harmed by the anti-seizure medication sodium valproate. It was a result of both research into the area, in part funded by the Epilepsy Research Institute, and the families’ tireless campaigning efforts which led to these recommendations. Despite this, research into Reproduction & Hormones continues to be a hugely underrepresented area in the field of epilepsy.
I want to help build a community of people from different clinical and scientific backgrounds to address key questions associated with the risks of taking ASMs during pregnancy or the influence of hormonal changes on seizure generation. The expertise is there, we just need to bring a task force group together to share resources, skill sets and ideas to radically advance research in this important area.
What do you hope the Institute’s Reproduction and Hormones task force group will achieve for people affected by the condition?
We want to ensure what happened with sodium valproate doesn’t happen again. By building a strong network of clinicians, fundamental scientists, public health workers and industry experts in this area, we will work together to ensure people living with epilepsy are able to make informed decisions on their treatment options and are clear on which ASMs are harmful to child health.
The theme encompasses reproduction in both women and men, as well as hormonal changes throughout the lifespan, and so advancing research in this area could be of huge benefit for people living with epilepsy and their families. If you’re a researcher and interested in becoming involved in the Task Force group, leave a comment on this post on The Hub (the Institute’s online portal for researchers working in epilepsy and associated conditions).
What are your hopes for the future of epilepsy research?
I hope that future research will focus on identifying better, more personalised treatment options for children and adults with epilepsy. We can achieve this with the integration of fundamental science, clinical research and collaborations with industry. For example, I am a basic scientist with strong links with clinical epilepsy experts and together we have been actively working on the translational capabilities of my work. Through multidisciplinary collaboration we stand the greatest chance at shifting the dial for people living with epilepsy.
The Institute is extremely grateful to Dr McLeod for sharing her views, and expertise, with us on this important topic and we look forward to hearing how this vital research progresses.