Have you ever wondered how donating your own or a loved one’s brain tissue can help research? Understanding the causes and development of epilepsy is crucial for identifying effective treatments. Studying the human brain using post-mortem brain tissues from those who lived with epilepsy or mitochondrial disease offers an exceptional opportunity to start answering these questions and unravelling the epilepsy process.
Following consent and ethical approval, donated brain tissue can help researchers identify what specific regions within the brain, and specific populations of brain cells, are involved in the epilepsy process. For example, we can use laboratory techniques to determine which brain cells may appear faulty, or even absent, in epilepsy brain tissue compared to ‘healthy’ brain tissue donated from individuals who have died from unrelated causes. Determining which specialised brain cells are vulnerable in epilepsy is crucial for understanding how seizures may be generated, and the impact of those seizures on healthy brain tissue.
As well as better understanding the epilepsy process, discoveries from research using brain tissue could also be used to identify drug targets. Importantly, this could help in the development of new epilepsy treatments, or the repurposing of existing drugs for people living with epilepsy.
The development of new model systems (such as cell or mouse models) that ‘mimic’ epilepsy or related conditions are often guided by observations made in donated brain tissue. Specific populations of brain cells identified as being particularly vulnerable in an epilepsy condition can be targeted in model systems to improve the brain cell function. These model systems, which often would not exist without human brain tissue research, can then be used to further investigate the causes of the condition and potential treatments.
Whilst model systems of disease can be extremely useful, they currently do not exist for every epilepsy condition and often they do not ‘mimic’ the features of human disease. Therefore, donated brain tissue is currently the most valuable resource for researching the causes of many epilepsies. However, this can be particularly challenging for rare forms of epilepsy due to the lack of brain tissue donated for research purposes, partly due to the low number of individuals living with the condition and lack of awareness of donating brain tissue for research.
At the Wellcome Centre for Mitochondrial Research at Newcastle University, we are extremely grateful for the generous number of post-mortem brain tissues from those who lived with epilepsy or mitochondrial disease (as well as brain tissues from those who have died from non-neurological causes, to be included as controls). These donations are crucial for our mitochondrial epilepsy research. We would like to express our sincere gratitude to all the families who have considered the donation process.
Research into DNA polymerase gamma (POLG)-related mitochondrial epilepsy, characterised by hard-to-control childhood or adult-onset epilepsy, has been accelerated by brain tissue donation. In POLG-related epilepsy, a genetic change affects the normal function of mitochondria, the parts of the cell that generate energy. As brain cells require high levels of energy, these changes to mitochondria have a major impact on their function, altering electrical brain activity, resulting in frequent seizures. Using brain tissue donated from people with POLG-related epilepsy, we have identified changes in some specialised brain cells which may be involved in the disease process. We aim to find out how these changes cause seizures and importantly, how they could be targeted to prevent them.
Rather excitingly, we are also exploring new ways to model POLG-related epilepsy using surgical human brain tissue, ethically donated from people having brain surgery to remove tumours or epilepsy tissue. We have a method that keeps small samples of brain tissue ‘alive’ in a laboratory environment, which allows us to investigate the conditions and treatments that cause and prevent seizures. This human model system, used by many researchers to model other forms of genetic epilepsy, offers a unique opportunity to study mitochondrial epilepsy, complementing our research using donated post-mortem brain tissue.