Preventing and Treating Epilepsy, Brain
Degeneration and Psychiatric Disease Following a
Brain Injury
Targeting Tau Phosphorylation to Treat and Prevent Acquired Epilepsy,
Neurodegeneration and Neuropsychiatric Disease Following a Brain Injury
Chief Investigator: Professor Terence O'Brien, Associate Professor Christopher
Hovens, Dr Nigel Jones
Lead Organisation: The University of Melbourne
TAC Neurotrauma Funding: $178,866
Project Start Date: 1 March 2011
Project Summary:
This project will explore an entirely new approach to the prevention and treatment of
epilepsy and the associated mental health disorders following a brain injury. This
involves inhibiting pathological forms of the Tau protein, which has been implicated
in the development of epilepsy and neurodegeneration. The drug that will be tested in
this study, sodium selenate, has already been demonstrated to be safe and well
tolerated in humans, meaning that a positive result from these studies could be
expediently translated into clinical studies.
Our work to date has demonstrated that treatment sodium selenate specifically
enhances the activity of the Tau protein phosphatase, PP2A leading to inhibition of
the pathological hyperphosphorylation of Tau which likely plays an important role in
the neurodegeneration that develops following a brain injury. Strongly supporting a
role for pathological Tau in epilepsy we have found that sodium selenate is effective
in suppressing induced seizures in a variety of rodent models. The current study will
extend this line of translational research to establish:
1. That treatment with sodium selenate is effective at suppressing spontaneous
seizures in rat models of epilepsy following a brain insult (i.e. post-kainic acid status
epilepticus and fluid percussion injury);
2. That treatment with sodium selenate is effective at inhibiting epileptogenesis and
neurodegeneration following a range of acquired brain insults in rat models (i.e.
kindling, post-kainic acid status epilepticus and fluid percussion injury).
3. Treatment with sodium selenate will mitigate the increased tissue expression of
total and phospho tau following a brain insult, with and without the development of
epilepsy.
Publications:
(as at Apr 2012)
JONES N, NGUYEN T, CORCORAN N, VELAKOULIS D, CHEN T, GRUNDY R, O'BRIEN TJ,
HOVENS C. Targeting hyperphosphorylated tau with sodium selenate has preclinical anti-epileptic
effects. Neurobiology of Disease 2012;45:897-901.
Presentations:
None
(as at Apr 2012)