This fellowship is a crucial steppingstone in my research career, as I become an independent investigator in the field of genetic epilepsies. The techniques I am developing offer so much potential for translation, from understanding how some faulty genes may cause epilepsy, to testing novel therapies and drugs on developing human neurons. I’m really excited about the advances in new knowledge my method offers neurologists and people affected by epilepsy, and hope that I can make a real difference.
Dr Faye McLeod
Early-onset genetic epilepsies 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. This makes them extremely challenging to study. Dr McLeod and colleagues have established a way to maintain developing human brain tissue in a laboratory environment, enabling them to alter genes of interest, and thereby study the consequences on the developing brain. They will now translate this into a clinically applicable tool for investigating disease mechanisms in genetic epilepsy.
The researchers will generate so-called “organotypic cultures” which are small pieces of a developing human brain that are kept in a dish. The cultures can be kept for approximately 2-3 months, during which time, the brain cells are well preserved. This new approach will be used to investigate how certain genes affect early brain development. Initially, this work will focus upon one gene, called STXBP1. It is one of the most common single-gene epilepsies and has an overlapping role with many other epilepsy risk genes.
The project will extend our understanding of how STXBP1 mutations cause early-onset epilepsy. It will also lay the groundwork for much more, because this is a highly adaptable method that could readily be used to investigate any genetic epilepsy.
Around 1 in 2,000 babies born in the UK have genetic epilepsy. This research will mean that parents and doctors will be able to provide clear explanations about the pathological significance, initially, of STXBP1 variants, and in due course, about any gene variant that is suspected of causing a developmental epilepsy. This will aid clinical diagnosis and suggest optimal therapeutic options.