24 Aug 2018

Epilepsy research success in State Government funding

Alfred epilepsy specialists. L-R: Dr Genevieve Rayner, Prof Patrick Kwan, Dr Piero Perucca, Dr Hugh Simpson, Dr Anne McIntosh, Dr Prash Puspanathan, Ms Shobi Sivanthamboo, Dr Andrew Gleason, Dr Anita Vinton, Dr Mark King, Dr Lyn Millist, Prof Terry O'Brien, Dr Anna Willard, Dr Lucy Vivash.
Professors Terry O'Brien and Patrick Kwan in the Department of Neuroscience were successfully awarded Victorian State Government grants each worth $100,000 this week. Their submissions were selected by the Department of Health and Human Services as part of its ‘Healthier Lives, Stronger Economy: Victoria’s Health and Medical Research Strategy 2016-20'. The projects are:

Brain glutamate imaging by ultra-high-field MRI for prediction of post-stroke epilepsy

Professor Patrick Kwan, who heads the Epilepsy and Personalised Medicine research group within the Department of Neuroscience, will lead a research study using an innovative technique called GluCEST to predict patients who are at risk of developing post-stroke epilepsy. It is estimated that 10% of patients develop epilepsy after stroke, but there is no reliable biomarker to identify those at risk. Glutamate is a chemical in the brain which becomes elevated after stroke. It has a significant role in initiating and sustaining seizures.

Traditionally measuring brain glutamate requires taking a biopsy, which is invasive for patients. The advent of ultra high-field Magnetic Resonance Imaging called 7T MRI allows mapping of whole brain glutamate non-invasively using GluCEST.

Professor Kwan, who is head of Epilepsy at the Alfred Hospital and the Royal Melbourne Hospital, will oversee the recruitment of patients from both hospitals who will undergo 7T MRI seven to 30 days after stroke and will be followed up for two years or until epilepsy develops.

With an ageing population and improved stroke survival, the number of people with post-stroke epilepsy is set to rise, placing increasing burden on society. It is hoped the study's findings will enable effective monitoring of stroke survivors and assist with the selection of patients at risk for future clinical trials.

A new treatment for adults with Refractory Absence Seizures

Professor Terence O’Brien, director of Neurology at the Alfred Hospital and head of the Department of Neuroscience, will lead a research project performing an early phase clinical trial to evaluate the safety and effectiveness of a new oral drug treatment (PRAX-944) in patients with refractory absence epilepsy. These seizures are brief lapses of awareness, sometimes with staring, which are often mistaken for daydreaming. Unfortunately the seizures cannot be adequately controlled as they are resistant to the effectiveness of currently available drug treatments. This has devastating effects on the patient's everyday living, in particular making it difficult to work and study effectively. It is estimated that there are 650 to 1000 patients with refractory absence epilepsy in Australia.

The study will enrol 12 patients with the disease to determine if a specific dose range of PRAX-944 can provide a therapeutic benefit. This will be determined by the use of a non-invasive clinical test known as EEG (electroencephalogram) which involves placing electrodes on patients’ scalps and recording brainwave activity. The project is a collaboration between The Alfred and neuroscience biotechnology company, Praxis Precision Medicines.

It will be one of the first trials to be performed in the new Clinical Trials Neurology Facility at the Alfred Hospital. It is a key example of the purpose of this new facility – to test the safety and effectiveness of novel treatments developed in the laboratory in the clinical setting in patients who have neurological conditions, known as ‘first-in-disease’ trials. The new treatment has demonstrated robust efficacy in pre-clinical laboratory models of absence epilepsy. To date 135 healthy volunteers have received single and multiple doses of PRAX944, which has been safe and well tolerated.

This particular drug treatment came about from one of the major challenges identified and faced by epilepsy specialists in a subgroup of patients with epilepsy that results in absence seizures.

Professor O'Brien is internationally recognised as one of Australia’s leading clinical and translational neuroscientists.

For the State Government's media release see https://www.premier.vic.gov.au/backing-our-brightest-medical-researchers/

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