Epilepsy research - Precision-based management

The goal is to demonstrate that integration of genomics into the clinical care of refractory epilepsy patients will significantly improve their healthcare and show that this can be delivered using available resources effectively and efficiently. This project involves the creation of a diagnostic genomic testing pathway for known genes associated with epilepsy.

The mission will be accomplished by creating a diagnostic algorithm which incorporates accessible genomic testing for the treating neurologist, a multi-disciplinary approach for report generation, enabling a clinically meaningful report to the neurologists as well as individualised reports to patients. This process is supported by a genetic counsellor working with the research team and treating neurologists. By better understanding the cause of epilepsy, a more precision-based approach to treatment can be achieved.

Twin studies are valuable to dissect the genetic and environmental influences to better understand these complex inheritance patterns: nature, nurture of both? Genetics can be put aside if we study identical twins, enabling a focus on environmental factors. One quarter of all identical twin pairs, in which at least one twin has epilepsy with no specific genetic cause, are discordant for epilepsy. In these twins, environment must be a major cause of the disorder.

Our research focus is to move from symptomatic treatment for patients, which occurs in a reactive fashion, to a more proactive treatment approach of developing innovative therapeutic strategies based on the underlying pathology. RNA therapeutics, such as miRNAs in epilepsy, hold great promise for better understanding the cause and for the development of novel drug targets to improve the outcome of this debilitating disorder.

This research will be in collaboration with the Centre for RNA in Neuroscience- Queensland Brain Institute, working to develop new RNA based therapeutic interventions for neurological disorders.

Visit the Centre for RNA in Neuroscience website

Epigenomics is the study of changes in gene expression without changes to the DNA sequence. Twins studies are an ideal paradigm to help differentiate between the three major components of phenotypic variation: genetics, shared, and non-shared environment. The discordant monozygotic twin model provides an elegant study design that controls for shared genetic and environmental factors, enabling a greater focus on the non-shared environment.

Almost one third of epilepsy patients have to endure a “medication odyssey” in the hope of finding an effective treatment. To shorten or alleviate this burden, brain organoids can created from pluripotent stem cells derived from the blood cells of epilepsy patients that are drug responsive or drug refractory.

We next examine the brain organoid activity patterns to discover drugs and drug combinations that are effective in treating the drug resistant patients (using the responsive ones as controls). We envisage that this unique approach will dramatically shorten the “medication odyssey” that epilepsy patients have to endure without finding an effective treatment.

This project is in collaboration with Prof Ernst Wolvetang from The University of Queensland Australian Institute for Bioengineering and Nanotechnology.

To utilise genomic and neurological expertise to improve the diagnostic pathway and to facilitate precision-based management of patients with neurological conditions.  A neuro-genomics service supports the complex process of assessment, testing and return of results, in order to facilitate ongoing care for the individual and their family, in close conjunction with their treating neurologist. This genomic information will underpin the era of precision medicine, which holds great promise for treatment advances such as gene-specific therapy, where genomic information can be used to better treat or cure disorders.

The goal is to demonstrate that this model of care in drug resistant epilepsy patients will significantly improve their healthcare and show that this can be delivered using available resources effectively and efficiently.

This singleton project utilises brain, buccal and blood derived samples from temporal lobe epilepsy patients to look at genes and genetic pathways where the epigenetic state links with epilepsy. By comparing different samples, we will be able to address the issue of tissue specificity in epigenomic studies. This project is in collaboration with A/Prof Jeff Craig, Centre for Molecular and Medical Research, School of Medicine, Faculty of Health, Deakin University.

This project provides a novel approach to deepen our understanding of phenotypic expression of idiopathic epilepsies by studying discordant monozygotic twins. The aim of this project is to focus on generating peripheral biomarkers for idiopathic epilepsies to aid in the diagnosis of idiopathic epilepsies and also act as specific markers for idiopathic epilepsy subtypes. The long-term hope of a peripheral biomarker will be the development of disease-modifying treatments. This project is in collaboration with A/Prof Jeff Craig, Centre for Molecular and Medical Research, School of Medicine, Faculty of Health, Deakin University.

This project builds the resource of an epilepsy twin cohort in Queensland and investigates the role of complex and non-traditional inheritance patterns through twin studies.