Epilepsy and Neuropharmacology Research Group
2018 O’Brien (epilepsy, neuropharmacology) group. L-R: Professor Terry O’Brien, Ms Emma Braine, Mr Michael x, Dr Kim Powell, Dr Pablo Casillas Espinosa, Mr Rafael Smith, Dr Idrish Ali, Mr Jack Germaine, Dr Loretta Piccenna
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.
Current Project Funding
Selected Recent Publications
- 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.