During last week’s WCMR ‘Research in Progress’ meeting, we heard from first year PhD student Laura Smith who talked about her research project that aims to understand the mechanisms of epilepsy in Alpers’ syndrome. Here, Laura tells us more about her work funded by the Ryan Stanford Appeal.

Mitochondria have their own DNA which is highly important for a number of processes including oxidative phosphorylation, an essential energy-producing pathway. DNA polymerase gamma (POLG) is responsible for producing new mitochondrial DNA within cells. However, mutations in the POLG gene, when inherited from both parents, can cause POLG to become faulty resulting in a loss of mitochondrial DNA. This makes it difficult for cells to produce energy, ultimately leading to cell death.

Alpers’ syndrome is a severe paediatric mitochondrial disease which affects approximately 1 in 100,000 individuals and ~90% of cases are caused by inherited POLG mutations. In Alpers’ syndrome patients, there is a loss of mitochondrial DNA specifically within the brain which causes a range of neurological symptoms, and in the liver which often leads to liver failure. Unfortunately, the loss of mitochondrial DNA is so severe it results in premature death, usually within the first two decades of life.

Alpers’ syndrome patients typically experience increasingly frequent seizures which often cannot be controlled by medications. Therefore, it is critical to understand the mechanisms causing such devastating seizures. This includes identifying the specific cells within the brain that are dysfunctional and/or lost in Alpers’ syndrome. Important cells to investigate include interneurons, which are specialised brain cells that stop excessive electrical activity and prevent seizures from occurring. Astrocytes (image on the right) are another type of protective cell which help to control the environment in the brain to prevent seizures from occurring.

Interneurons and astrocytes can be investigated by analysing post-mortem brain tissue generously donated by Alpers’ syndrome patients. Hopefully this will provide an insight into ways to potentially therapeutically intervene to manage seizures in Alpers’ syndrome, and to help stop the progression of this devastating disease.