Understanding Epilepsy in Alpers’ Syndrome

As part of our WCMR science seminar series, we recently heard from Dr Laura Smith about her research that aims to understand the causes of epilepsy in a mitochondrial condition called Alpers’ Syndrome. Here Laura tells us more.

Dr Laura Smith

Alpers’ syndrome is a rare paediatric mitochondrial disease caused by changes in a gene called POLG1 which results in epilepsy that is difficult to control and neurological decline. The causes of epilepsy in Alpers’ syndrome are poorly understood and as such, a better understanding is important for identifying effective treatments for patients.

POLG1 mutations affect the function of mitochondria, the parts of the cell that supply energy. As cells within the brain are highly energy-demanding, impaired function of mitochondria in these cells severely disrupts brain activity leading to seizures.

By investigating brain tissue kindly donated by patients, we have identified changes to specialised brain cells which may be involved in the generation of seizures in Alpers’ syndrome. Our study revealed fewer ‘interneurons’ were present in Alpers’ syndrome brains compared to healthy control brains. Interneurons normally have an important role in managing electrical brain activity. Therefore, the loss of interneurons in Alpers’ syndrome brains may disrupt the controlled balance of electrical activity, increasing the risk of seizures occurring.

We have also recently identified changes to astrocytes, a second type of specialised brain cell which normally respond to high levels of electrical activity to support neurons and prevent seizures. Impaired function of astrocytes in Alpers’ syndrome may contribute to the development of seizures in patients.

Our research at the WCMR will continue to better understand the causes of epilepsy in Alpers’ syndrome and other mitochondrial epilepsies. Our work also offers hope for the wider epilepsy community since changes identified in mitochondrial epilepsy may be shared with many common epilepsies.

This work would not have been possible without the generous donation of brain tissue from patients with Alpers’ syndrome and POLG-related disease, and without funding from The Ryan Stanford Appeal.

You can read more about our Alpers’ syndrome research which was recently published in the journal Neuropathology and Applied Neurobiology by clicking here.

Laura has presented this work at a number of recent scientific meetings, including the 3rd FMS Post-Doctoral Symposium at Newcastle University where she was awarded 2nd prize for her talk.

Dr Laura Smith presenting her research at the Mito Medicine 2022 conference in Cambridge, UK.