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Vadlamudi Group - Clinical trials

Personalising Epilepsy Regimes with Stem cells and artificial Intelligence models for Superior Treatment outcomes (PERSIST)

This MRFF funded project will utilise cohorts of human induced pluripotent stem cell lines (hIPSC) derived from drug-responsive and drug-resistant epilepsy patients established across the two epilepsy research nodes (The University of Queensland and Monash University) and build on our collective expertise in generating hIPSC-derived brain organoids. We will also integrate our expertise in artificial intelligence models to further advance the algorithm.

We will use hiPSC-derived brain organoids and screen a library of approved drugs to identify those able to alter neural activity in a patient-specific model, train an artificial intelligence model that leverages both clinical and genomic data to assist drug selection, and validate treatment predictions in real-world clinical settings.

Demonstrating the utility of an epilepsy patient-specific in-vitro drug screening platform in combination with decision-making software offers substantive health benefits for patients, provides neurologists with an evidence-based medicine approach, reduces health care costs and has the potential to enable transformative new insights into the genetic drivers of epilepsy and drug-resistance, to inform new therapy development.

Visit the PERSIST website

Towards personalised care for epilepsy patients: Using a patient-specific, human organoid platform for disease modelling and drug screening

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.

Developing a Queensland neuro-genomics service to underpin the era of precision-based medicine

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.

Piloting a neurogenetics service for drug resistant epilepsy patients

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.

Genetic networks in epilepsy; A tissue specific approach

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.

The epigenetic and genetic landscape of idiopathic epilepsies: the testament of twins

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.

Genetics of epilepsy: A twin approach to complex and non-traditional inheritance patterns

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.

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