Epilepsy and Neuropharmacology Research Group
- Epilepsy, Neuropharmacology
2019 group: L-R: Dr Loretta Piccenna, Dr Andreas Pattichis, Ms Hue Mun Yong, Dr Andrew Neal, Dr Lubna Shakhatreh, Prof Terence O'Brien (Group leader), Prof Patrick Kwan, Dr Shobi Sivathamboo, Ms Crystal Li, Dr John-Paul Nicolo, Dr Pablo Casillas-Espinosa, Dr Marco Neri.
Absent - Dr Idrish Ali, Dr Anne McIntosh, Dr Andrew Gleeson, Dr Toby Winton Brown, Dr Lucy Vivash, Dr Ben Sinclair, Dr Josh Laing, Ms Emma Braine
Group Leader - Prof Terence O'Brien
Prof Terence O’Brien is a specialist in neurology and clinical pharmacology, with particular expertise in epilepsy and neurodegenerative diseases, neuropharmacology, pre-clincal and clinical drug development, and in-vivo imaging in animal models and humans.
E: email@example.com | T: +61 3 99030855 |
Find out more about Prof Terence O’Brien
Senior Research Officers
- Dr Anne McIntosh
- Dr Andrew Gleeson
- Dr Toby Winton Brown
- Dr Marco Fedi
Post-Doctoral Research Officers
- Ms Emma Braine
- Ms Sarah Barnard
- Dr Joshua Laing
- Dr Andreas Pattichis
- Ms Shobi Sivathamboo
- Ms Dana Jazayeri
- Ms Meghan Gollant
- Ms Jiehui (Lisa) Lu
- Ms Vivienne Chan
To be updated
The group’s research is broad based translational, covering both basic and clinical studies investigating to epilepsy and related areas, including traumatic brain injury and dementing disorders. The work has had two primary goals: 1. better understand the determinants of treatment response by identify biomarkers for treatment outcomes – imaging, electrophysiological, genomic and clinical, and to develop new treatment approaches. 2. To investigate the fundamental neurobiological basis of the neuropsychiatric and medical co-morbidities present in many patients with epilepsy and related conditions. We have a major focus on developing new treatments, testing them in pre-clinical studies, and then translating these into early phase clinical trials. The group integrated with the Department of Neurology in the Alfred Hospital, including the dedicated Neurological Clinical Trials Facility which has capacity for first-in-disease clinical trials.
for disease modification and prevention of the development of epilepsy
Current therapies for epilepsy are symptomatic, only suppressing the symptoms (seizures), but do not impact the development or progression of disease. Many groups around the world, including ours, are testing novel therapies to impact epileptogenesis, intervening very early in epilepsy development to limit the severity of disease, with some preclinical success. But most patients present at the clinic already experiencing seizures, so a more practical strategy would be to attempt to modify epilepsy disease progression. For this project, we will investigate whether our novel treatments can reverse epilepsy severity in a rat model of acquired epilepsy in cases of established epilepsy. We then evaluate if the animals are having less seizures, behavioural comorbidities and neuroimaging changes after the completion of treatment. If the results are positive, they would have major clinical implications in patients with already established acquired epilepsy. Moreover, the experimental drugs that we will be tested have a favorable safety profile in early phase clinical trials facilitating the translation of the results of this preclinical study into a clinical trial.
A biomarker is an objectively measured characteristic of a normal or pathologic biological process. The development of novel interventions to treat, cure, and prevent epilepsy would benefit greatly from the identification and validation of such biomarkers. In addition, identification of biomarkers may facilitate the development of novel interventions to prevent epilepsy; to prevent the occurrence of epileptic seizures, reverse progression of epilepsy, and potentially even cure epilepsy after it is established. This project will investigate blood- and brain-derived biomarkers of epileptogenesis (the development of epilepsy) and of disease progression of epilepsy using small animal models.
and the role of stress and early life trauma in patients with chronic epilepsy and psychogenic non-epileptic seizures
Depression and epilepsy are disabling disorders that are common in the community. Both disorders have been shown to have effects on the human body’s physiological response to stress. These effects have been identified in both the autonomic nervous system (responsible for immediate responses to stress) and the hypothalamic-pituitary-adrenal axis (which mediates longer-term stress responses). However, it is not known whether these effects occur through similar mechanisms, partly because previous research has not focused extensively on patients with both disorders. This project will broaden our understanding of stress physiology, and the enduring effects of early life trauma, in these disorders by assessing stress physiology in patients who have been admitted to hospital for assessment of seizures and have one or both disorders.
How does chronic epilepsy result in cardiac electrophysiological dysfunction?
- Chief Investigators: O’Brien TJ, Powell K, Dellbridge L, Pilowsky P, Royce C.
- Funding Source:NH&MRC Project Grant #APP1082215
- Funding Amount:$709,154
Human Epilepsy: Understanding biology to improve outcomes
- Chief Investigators: Berkovic SF, Jackson GD, Gecz J, Connelly A, Scheffer I, O'Brien TJ, Petrou S, Calamante F, Reid C.
- Funding Source:NH&MRC Program Grant #APP1091593
- Funding Amount:$16,110,300
Developing Transformative Therapies for Modifying or Preventing Epilepsies (U54): The Epilepsy Bioinformatics Study for Treatment (EpiBioS4Rx)
- Chief Investigators: Jerome Engel, Jr., Aristea Galanoupoulou, Solomon Moshé, Asla Pitkänen, Arthur W. Toga, Paul Vespa, Terence O’Brien.
- Funding Source:NINDS RFA-NS-16-012: Centers Without Walls for Collaborative Research in the Epilepsies.
- Funding Amount:$21,700,000 USD
A Phase 1a Open Labelled Study of Sodium Selenate as a Disease Modifying Treatment for Probable Behavioural Variant Fronto-temporal Dementia
- Principle Investigators: Terence O’Brien, Dennis Velakoulis, Charles Malpas, Lucy Vivash and Chris Hovens
- Funding Source:RMH Neuroscience Foundation.
- Funding Amount:$700,000
Targeting post-synaptic AMPA receptors for prevention and control of seizures in patients with supratentorial glioma: a pilot randomised controlled trial
- Chief Investigators:Neal A, Morokoff A, O’Brien TJ, Kwan P
- Funding Source:Eisai Pharmaceuticals
- Funding Amount:$602,400 ASD
- Human Epilepsy Project (HEP): New/recently diagnosed focal Epilepsy - observational study
- SK Life Sciences YKP3089C021: Open Label Phase III Focal Epilepsy Trial
- Zynerba: Phase II RCT of focal Epilepsy treatment using transdermal CBD
- GWEP: Phase II RCT of oral CBD study in Adults with Complex (Oral CBD)
- SP0982: Phase III RCT of Lacosamide in Primary Generalised Epilepsy
- Pegasus: Phase III RCT of Perampanel in Glioma Associated Seizures (Investigator Initiated Study)
- CuroNz Phase Ib study of NRP2945 in patients with stable photosensitive epilepsy
- Biscayne BNI-02-1b: Phase Ib study of Huperzine A
- MADERCT of Modified Atkins Diet in Epilepsy (Investigator Initiated)
- TEVA - 30056 Phase II RCT of monoclonal CGRP inhibitor for Episodic Cluster Headache Study
- TEVA - 30057Phase II RCT of monoclonal CGRP inhibitor for Chronic Cluster Headache Study
- INP-103Phase Ib study of Intranasal administration of L-dopa for Parkinsons Disease
- Abbvie PSPPhase IIa ABBV-8E12 RCT for Progressive Supranuclear Palsy (PSP).
- Phase Ib study of Sodium Selenate as a Disease Modifying Treatment for Probable Behavioural Variant Front-temporal Dementia (Investigator Imitated).
- Genentech study (GN39763): Phase IIb RCT as a disease modifying treatment for Alzheimer’s Disease
- Avanir AVA78635-786305: Phase IIa study for agitation in patients with Alzheimer’s Disease
- Liu S, Zheng P, Wright DK, Dezsi G, Braine E, Nguyen T, Corcoran B, Johnston LA, Hovens CM, Mayo JN, Hudson M, Shultz SR, Jones NC, O’Brien TJ. Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau. Brain 2016 139(Pt 7):1919-38. PMID: 27289302. [I.F. 10.103]
The first study to demonstrate the anti-epileptogenic effect in animal models of pharmacologically targeting hyperphosphorylated tau following a variety of epileptogenic brain insults.
- Oxley TJ, Opie NI, John SE, Rind GS, Ronayne SM, Wheeler TL, Judy JW, McDonald AJ, Dornom A, Lovell TJH, Steward C, Garrett DJ, Moffatt BA, Lui EH, Yassi N, Campbell BCV, Wong YT, Fox KE, Nurse ES, Bennett IE, Bauquier SH, Liyanage KA, van der Nagel NR, Perucca P, Ahnood A, Gill KP, Yan B, Churilov L, French CR, Desmond PM, Horne MK, Kiers L, Prawer S, Davis SM, Burkitt AN, Mitchell PJ, Grayden DB, May CN, O'Brien TJ. Endovascular stent-electrode array for minimally invasive high-fidelity chronic recordings of cortical neural activity. Nature Biotechnology 2016 Mar;34(3):320-7. doi: 10.1038/nbt.3428. Epub 2016 Feb 8. PMID: 26854476. [I.F. 41.514] (Cits = 27, GS Aug 2017).
The first demonstration that a implanted intra-vascular stent electrode recording array, “stentrode”, can chronically record high-fidelity brain activity that has the potential for application to control a bionic limb.
- Shultz SR, Wright DK, Zheng P, Stuchbery R, Liu S-J, Sashindranath M, Medcalf RL, Johnston L, Hovens CM, Jones NC, O’Brien TJ. Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury. Brain 2015 May;138(Pt 5):1297-313. [I.F. 10.226]. (Cits = 15, GS Sept 2016)
The first study to demonstrate that pharmacologically targeting hyperphosphorylated tau following an experimental traumatic brain injury can mitigate the long term neurodegenerative and neurobehavioural consequences.
- Epi4K and EPGP Investigators (*TJ O’Brien is an Epi4K Author). De novo mutation in epileptic encephalopathies. Nature 2013; 501(7466):217-21. [I.F. 38.597]. (Cits = 558, GS Aug 2016)
Reported for the first time the importance of de genetic novo mutations as a cause of epileptic encephalopathies. Also described the important concept of ”intolerant genes”.
- Cook MJ, O’Brien TJ, Berkovic SF, Murphy M, Morokoff A, Fabinyi G, D’Souza W, Yerra R, Archer J, Litewka L, Hoskings S, Lightfoot P, Himes D, Ruedebusch V, Sheffield D, Leyde K. Prediction of Seizure likelihood with a long-term ambulatory, implanted seizure advisory system in patients with drug-resistent epilepsy: A first-in-man study. Lancet Neurology 2013;12:563-71. [I.F. 23.92] (Cits = 223, GS Aug 2017)
The first to demonstrate fesiabilty of seizure prediction in humans, and first long-term ambulatory implanted intracranial EEG study, demonstrating the safety and efficacy in detecting seizures compared to traditional seizure diaries.