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Discovery of new step in how brain cells work could lead to new therapies for epilepsy

June 30, 2020

Dublin, Tuesday, 30 June 2020: Researchers have identified a critical new step in how brain cells function in people with one of the most common forms of epilepsy. This could lead to new treatment approaches for people with drug-resistant epilepsy.

The study was led by researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, hosted by RCSI University of Medicine and Health Sciences with colleagues at Severo Ochoa-Centre for Molecular Biology (CBMSO) of Madrid and Institute for Research in Biomedicine (IRB) of Barcelona. The research is published in Brain.

Changes in gene activity are known to be important in the development of epilepsy. Normally, a molecule called messenger RNA is produced when a gene is active. This becomes the template for the production of the proteins that brain cells use to function. A critical step is the addition of a short sequence called a poly(A) tail. This has never been studied before in epilepsy. The team discovered that this tailing process (polyadenylation) is dramatically altered for about one third of the genes of someone with epilepsy, changing protein production in the brain.

"Our discovery adds another piece to the puzzle to help us understand why gene activity is different in someone with epilepsy," said Dr Tobias Engel, FutureNeuro Investigator and Senior Lecturer in the School of Physiology and Medical Physics at RCSI. "It is remarkable that so many active genes in the brain show a change in this polyadenylation process. We believe that this could ultimately lead us to new targeted treatments, allowing us to investigate if we could stop a person from developing epilepsy."

Epilepsy is one of the most common chronic brain diseases, affecting over 65 million people worldwide. While current drug treatments are usually effective in suppressing seizures, they do not work in one third of people with epilepsy and have no effect on the underlying causes of the disease.

"Regulated poly(A) tailing of messenger RNAs is a step in gene expression regulation barely explored in brain diseases, and our study should foster its investigation in other brain conditions in which gene expression alteration is suspected," said Dr José Lucas, Research Professor at Severo Ochoa-Centre for Molecular Biology of Madrid.

Prof. David Henshall, Director of FutureNeuro and Professor of Physiology in the School of Physiology and Medical Physics at RCSI, said, "Our aim in FutureNeuro is to provide faster diagnostics, precision therapeutics and eHealth enabled solutions for those with chronic and rare neurological diseases. This research is a great example of how understanding basic mechanisms of a disease can guide us to new targets for treatment."
-end-
This research was co-funded by the Health Research Board, H2020 Marie Sk?odowska-Curie Actions Individual Fellowship and from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement.

About FutureNeuro

FutureNeuro is the SFI Research Centre for Chronic and Rare Neurological Diseases. We aim to change the patient journey through research informed by the needs of both patients and neurologists. This includes developing rapid and accurate tools for diagnosis, the development of therapies to correct damaged brain networks, technologies to enable patients to monitor their own health and well-being, and linking this to Ireland's national imaging, diagnostics and eHealth infrastructure.

We are multi-disciplinary, inter-institutional and working with industry, patient organisations and the health service to transform the lives of patients in Ireland and worldwide.

About RCSI University of Medicine and Health Sciences

Ranked number one globally for Good Health and Well-being in the Times Higher Education (THE) University Impact Rankings 2020, RCSI University of Medicine and Health Sciences is an international not-for-profit university, with its headquarters in Dublin.

RCSI is exclusively focused on education and research to drive improvements in human health worldwide. It is among the top 250 universities worldwide in the THE World University Rankings (2020) and its research is ranked first in Ireland for citations. RCSI has been awarded Athena Swan Bronze accreditation for positive gender practice in higher education.

Visit the RCSI MyHealth Expert Directory to find the details of our experts across a range of healthcare issues and concerns. Recognising their responsibility to share their knowledge and discoveries to empower people with information that leads them to better health, these clinicians and researchers are willing to engage with the media in their area of expertise.

RCSI

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