CIA Professor Patrick Kwan (left) and CIB Dr Ben Rollo (right), both in the Central Clinical School’s Department of Neuroscience. The team includes CIC Dr Chris Langmead (Drug Discovery Biology, MIPS), CID Dr Katie Ayers (MCRI) and CIE Dr Alexander Harris (UniMelb) |
Epilepsy is a severe neurological disease which affects over 70 million people globally. Despite a concerted effort to identify new anti-seizure medications (ASMs) over the last 25 years, epilepsy remains uncontrolled in 30% of individuals, a condition known as drug-resistant epilepsy. Therefore, there exists an urgent unmet clinical need to identify new effective drugs to treat epilepsy.
This project will take stem cells from both healthy individuals and those with drug-resistant epilepsy, and grow their stem cells in vitro into neurons. The researchers will test the ability of a library of drugs to suppress the abnormal activities of these neurons. The process will enable rapid assessment of new effective drugs that target drug-resistant epilepsy at a speed and scale not possible with conventional animal methods.
Currently, the principal method for assessing ASM candidates relies on the successful treatment of induced seizures in rodent models of epilepsy. However, these rodent models have fundamental limitations; they do not faithfully recapitulate the human disease nor the potential efficacy of the ASM being tested and are both costly and time consuming.
The group will pioneer human epilepsy personalised medicine models to screen candidate ASMs in high-throughput. These models will comprise neurons differentiated from induced pluripotent stem cells (iPSCs) obtained from healthy individuals and individuals with drug-resistant epilepsy.
To validate these epilepsy models, spontaneous and induced epileptic neural activity will be generated and electrophysiological properties will be assessed. Validity as a drug screening tool will be assessed by treatment with currently available ASMs in drug-responsive and non-responsive iPSC-derived neurons. Identification of first-in-disease drugs will be achieved by screening drug-resistant neural cultures with an approved drug library.
New drug candidates will be selected, based on their ability to restore normative neural activity during both spontaneous and epileptic conditions in drug-resistant genetic backgrounds. This innovative personalised medicine model will enable rapid first-line assessment of candidate ASMs in speed and scale not possible with conventional methods.
Learn more about Prof Patrick Kwan's research: www.monash.edu/medicine/ccs/neuroscience/research/kwan-group
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