Neuroscience researchers receive $1.45M from US Department of Defense for research on Post-Traumatic Epilepsy

Dr Idrish Ali (left) & Dr Pablo Casillas-Espinosa (right)

by Dr Loretta Piccenna

International funding totalling $1,450,575 from the US Department of Defense (DoD) Epilepsy Research Program has been awarded to early career researchers - Dr Idrish Ali (EP200033) and Dr Pablo Casillas-Espinosa (EP200022) - within the Department of Neuroscience, to each individually advance translational research on Post-Traumatic Epilepsy. This will further efforts to improve detection and minimise related health risk factors in individuals affected, especially Service members and Veterans. 

Post-Traumatic Epilepsy is the most common cause of new-onset epilepsy in young adults. Post-Traumatic Epilepsy is a serious and disabling long-term consequence of a traumatic brain injury (TBI).

Post-Traumatic Epilepsy occurs in around 20% of people who experience a traumatic brain injury and is associated with significant increased morbidity (depression, cognitive and social challenges) and mortality. Post-Traumatic Epilepsy produces a large, lifelong burden affecting individuals’ quality of life, their family and additionally, has an impact on the costs to the local community and wider society.

The cause of Post-Traumatic Epilepsy is still unknown, but increasing evidence points to inflammation of the brain following a traumatic brain injury, which results in changes to its structure and function, and the development of epilepsy. To improve the physical, social and psychological wellbeing of individuals, it is critical to understand how the disease occurs and progresses. 

Reliable identification of patients at high risk is an urgent unmet clinical need. There is also a pressing need for novel preventive treatments. However, there are no biomarkers to effectively target these preventive therapy trials. Any trials investigating new preventive therapies would require large numbers of participants, targeting all cases of TBI, and long follow-up times, which limits the feasibility of any such clinical trial. 

The Idea Development Award under the Epilepsy Research Program was established in Fiscal Year 2015 as part of the Congressionally Directed Medical Research Programs administered by the United States Department of Defense (DoD). The Epilepsy Research Program aims ‘is focused on understanding who is affected by Post-Traumatic Epilepsy in the military in order to understand who may be most vulnerable and how it affects the individual’s prognosis and risk factors.’ Dr Ali and Dr Casillas-Espinosa will help the program to achieve this aim and additionally further establish their research careers in this area.

Measuring inflammation in brain and blood for predicting risk of post-traumatic epilepsy 

Dr Idrish Ali (BPharm, MS, PhD), an established neurobiologist and post-doctoral researcher in the Epilepsy and Neuropharmacology group, will focus on investigating inflammation as a biomarker to predict the development of Post-Traumatic Epilepsy and neuropsychiatric comorbidities in an animal model using neuroimaging and inflammatory proteins in blood at multiple time points. 

“The approaches used in this study are highly translational, and readily applicable in the clinical post-TBI care setting. If successful, our study could inform clinical trials and practices in the near future to include neuroinflammatory outcomes in the initial assessments,” commented Dr Ali.

The project will be supported by funding of $677,949.17 over 3 years, and involve a team including A/Professor Nigel Jones, Professor Terence O’Brien, Professor Stefanie Dedeurwaerdere, A/Professor David Wright and Dr Lucy Vivash.

Reversing Post-Traumatic Epilepsy

Dr Pablo Casillas-Espinosa (MD, PhD) is a NHMRC Peter Doherty Early Career Fellow who leads a newly established research group in the department. His project will investigate if a novel disease-modifying treatment, sodium selenate (protein phosphatase 2A enhancer), will be able to “reverse” the development of epilepsy and its neuropsychiatric problems following a traumatic brain injury using an animal model. Treatment of people with Post-Traumatic Epilepsy is difficult as prognosis is variable and some patients are not responsive to currently available treatments for epilepsy. The project will also find prognostic biomarkers for Post-Traumatic Epilepsy using multi-omics and advance computational biology approaches to help identify patients who are high risk and to understand the progression of the disease and response to treatment. 

The project will be supported by funding of $772,625.50 over 3 years, and integrate experts across different disciplines including Professor Terence O’Brien (clinical neurology), A/Professor Sandy Shultz (neuroscience), A/Professor Ralf Schittenhelm (proteomics), A/Professor Nigel Jones (neuroscience), Dr Anup Shah (bioinformatics), Dr Alison Anderson (bioinformatics), and Dr Enzo Huang (bioinformatics). 

“We have preliminary data that has shown sodium selenate treatment had an enduring effect in an animal model of Post-Traumatic Epilepsy demonstrating a reduced frequency of spontaneous recurrent seizures and mitigated memory and sensorimotor deficits, which is the first time this has been shown for any pharmacological treatment.

“Importantly, selenate has already been shown to have a favourable safety profile in early phase clinical trials for other diseases, facilitating the translation of the results of this preclinical study into a clinical trial of disease-modifying therapy for Post-Traumatic Epilepsy,” commented Dr Casillas-Espinosa.

Head of Department, Professor Helmut Butzkueven said “these funding outcomes were really exciting news that will have a significant impact on improving the quality of life of military, veterans and people in the community who experience Post-Traumatic Epilepsy. The individual projects will contribute important knowledge that could substantially improve the management of people with PTE and help target patients for specific treatments for future clinical trials." 

"It is also great to see two of our early career researchers be supported to establish themselves in the translational neuroscience research field as the next generation of experts."