With the city of Gotham in peril, Batman lies in wait, ready to jump to the rescue as soon as he sees the bat signal. Most of the time he is hidden out of site and the city goes about its normal business. But, when something bad happens, Batman is always there, springing in to action. My work will create the brain’s very own Batman, hidden for most of the time, but always ready to jump at the bat signal and prevent seizures from happening when the brain moves to an epileptic state.
Let’s set superheroes aside for a second and talk about science. My lab will focus on a naturally-occurring family of molecules called microRNAs, exploring how we can use these to treat epilepsy. MicroRNAs exist in our cells to help them to generate the correct amounts of proteins from which the cells are made. One of the many interesting features of microRNAs is that they seem to be closely linked to epilepsy.
Indeed, my previous work showed that we can inhibit the function of certain microRNAs and use this to stop seizures. Furthermore, the amounts of some microRNAs are closely linked to seizures and can change dynamically when seizures happen. Measuring the level of a carefully selected microRNA might even be able to predict an oncoming seizure before it happens.
It follows that certain microRNAs could provide a very specific signal, showing when a brain cell (or group of cells) are about to participate in a seizure. Perhaps then, we can use this as a bat signal, to trigger some kind of anti-seizure treatment.
The first goal of my lab will be to characterise these microRNAs signatures in detail, understanding exactly which cells they come from and how this relates to seizure generation.
If we are able to understand the exact relationship between microRNA changes and seizures, then we can exploit this to create on-demand microRNA-dependent epilepsy therapies.
The microRNA will be the bat signal, and now we need to create Batman.
One of the most promising approaches in epilepsy therapeutics is the use of gene therapy techniques. Indeed, University College London, where I will be based, is a leader in this field, with several excellent gene therapy research groups.
Recent developments have shown that gene therapies can even be incorporated into dynamic systems, that can switch on and off in response to seizure activity in the brain. It’s also been shown that microRNAs (our bat signal) can be used to control gene therapy, but this has never been tried in epilepsy.
I want to combine my new knowledge of microRNA signatures of epilepsy with these cutting-edge gene therapy approaches, to create a therapy that is dynamically switched on and off by the changes in microRNA that happen leading up to a seizure. This is a new kind of control mechanism, which might be able to act as Batman and prevent the seizure before it can get started.
In the long run, my lab will focus on finding novel ways to exploit microRNA for therapies in different kinds of epilepsy.
A big hope for gene therapy is that it will represent a permanent treatment for certain types of epilepsy, meaning that people should not have to keep taking anti-seizure medications.
Because gene therapy only targets a small part of the brain, the side effects are likely to be much less noticeable than taking anti-seizure drugs, which impact the whole of the brain. However, classic gene therapy does involve permanently reducing the activity of the targeted brain area, and this could still have small impacts on things like memory. By using microRNA biosignatures to control gene therapy, I hope to add a new control mechanism that allows the gene therapy to be switched on and off dynamically, whenever it is needed.
I’m really looking forward to updating Epilepsy Research UK’s supporters on the progress of this research in the coming years. But for now….TO THE BATMOBILE!
-Dr Gareth Morris
You can read more about Dr Gareth Morris’ project on using microRNA biosignatures ss sensors for precision gene therapy here.