Researchers at the University of Queensland (UQ) are exploring the potential of spider venom to treat drug-resistant epilepsy in children. Supported by a $4.1 million grant from the federal government's Medical Research Future Fund, the four-year study will test spider venom molecules against brain tissue derived from individual epilepsy patients. This innovative approach aims to develop personalized medications for various genetic epilepsies.
Venom-Based Drug Discovery
Professor Glenn King of UQ's Institute for Molecular Bioscience, who has been working on venom-based drugs for epilepsy since 2017, explained that the study would test spider venom molecules against brain tissue made from the blood of individual epilepsy patients. Scientist Selin Pars, from UQ's Australian Institute for Bioengineering and Nanotechnology, is creating brain "organoids" from patient blood samples. These lentil-sized organoids contain key cell types of the human cortex, including neurons and glia, and will be used to test the venom peptides.
Dr. Pars highlighted the specificity of one spider venom peptide for a single protein, stating, "What I'm excited about in this project is that a spider venom peptide we will be testing is very specific for this one single protein. We need therapies to be more specific..."
Promising Preliminary Results
Preliminary research has shown that a peptide found in the venom of a large West African tarantula (Heteroscodra maculata) reduces the firing of neurons in brain tissue derived from children with specific types of genetic epilepsy. Professor King's team will also explore other venom molecules to treat different genetic epilepsies, such as those caused by mutations in the KCNH1 and KCNQ2 genes.
Professor King noted that a tarantula peptide, known as Hm1a, has been shown to reduce seizures and early death in mice with Dravet syndrome. "Because of the mechanism of action, we've surmised that it might work for a bunch of other epilepsies as well," he said.
Addressing Unmet Needs in Epilepsy Treatment
Epilepsy affects more than 250,000 Australians, with about 30% of cases considered refractory, meaning medication fails to control seizures. For these individuals, the impact of epilepsy can be devastating, leading to physical injury, memory problems, and loss of independence. More than half of people with epilepsy experience anxiety and depression, and the stigma associated with the condition remains high.
Epilepsy Queensland's interim CEO Sandi Rodiger emphasized the hope that research in this area provides for more effective treatments, particularly for patients with refractory epilepsy and their families.
Organoids for Personalized Medicine
The use of brain organoids in drug discovery is an emerging area in science. University of Sydney medicinal chemist Michael Kassiou, who is not involved in the venom research, noted that organoids are better than animals at testing the potential effectiveness of an experimental drug as a treatment for human disease. "Obtaining a favorable drug response from an organoid that mimics human disease is likely to be more predictive of clinical outcomes than results from animal models," Professor Kassiou said.
Future Directions
While the research is promising, Professor King cautioned that much more work is needed before venom-derived drugs reach patients with seizures. The drugs would likely need to be administered via injection or an implantable device. "We're still many years away from potentially having these drugs delivered to patients. We don't want to give false hope. We want to be realistic and say: 'We're working on the problem, we've got some leads, it's going to take some time to get to the clinic.'"
