Study unveils critical insights in understanding post-traumatic epilepsy

A new international study has unveiled critical insights in understanding post-traumatic epilepsy (PTE), a condition that can develop following traumatic brain injury. Led by researchers at FutureNeuro, the Research Ireland Centre for Translational Brain Science and RCSI University of Medicine and Health Sciences and published in Theranostics, the study highlights the important role played by a receptor in the brain called P2X7.

It suggests how we could both reduce epilepsy risk and predict which patients are most at risk of developing PTE by targeting this receptor. Traumatic brain injury (TBI), caused by physical trauma to the head, is one of the leading causes of long-term disability and death worldwide. PTE is a common outcome, characterized by recurring seizures that profoundly impact quality of life. At the moment, up to 30% of PTE patients do not respond to existing medications, and no treatments are currently available to predict or prevent the development of epilepsy following traumatic brain injury.

The collaborative research, led by FutureNeuro and RCSI, involving institutions including Trinity College Dublin, CIC biomaGUNE, Soochow University, and the Institute for Stroke and Dementia Research, identifies the P2X7 receptor as a key driver of abnormal brain activity after brain injury. In preclinical models, blocking this receptor shortly after injury significantly reduced brain hyperexcitability, minimized brain damage, and improved behavior, underscoring its promise as a therapeutic target for preventing epilepsy.  By looking at the activity of the P2X7 receptor using a PET scan, the authors also suggest a potential new diagnostic tool. The uptake by the brain of a specialized P2X7 receptor tracer shortly after injury was found to correlate with seizure risk weeks later. This tool could help clinicians identify at-risk patients early, enabling timely and tailored interventions.

Dr. Tobias Engel, FutureNeuro Investigator and Senior Lecturer in the RCSI Department of Physiology and Medical Physics, commented: "Traumatic brain injury is a major cause of epilepsy in adults, with many patients unable to benefit from existing anti-seizure treatments. Our research has identified the P2X7 receptor as a promising new target, offering the potential to prevent epilepsy before it develops, sparing patients from seizures and the burdens of ongoing medication." 

"While additional research is required to confirm our findings and explore their application in clinical settings, we've made a significant step forward in addressing the unmet need for early intervention in post-traumatic epilepsy" added Dr. David Loane, Associate Professor in Neuroscience at Trinity College Dublin. "This was made possible through extensive multidisciplinary collaboration, demonstrating the power of shared expertise in advancing epilepsy research."

By identifying a potential therapeutic target and a corresponding predictive diagnostic tool, this research opens new avenues for personalized care, improved outcomes and a better quality of life for patients with traumatic brain injury at risk of epilepsy."

Dr. Jordi Llop, Principal Investigator at CIC biomaGUNE

The study involved extensive multidisciplinary collaboration, including key industry partners, Janssen and Affectis Pharmaceuticals. Funded by Research Ireland, the project leveraged diverse expertise to tackle the complex challenges of traumatic brain injury and epilepsy.