Spider venom could hold the key for drug-resistant epilepsy

New research by the Royal Brisbane and Women’s Hospital (RBWH) and The University of Queensland (UQ) is harnessing the power of spider-venom peptides to provide precision therapy for drug-resistant genetic epilepsies.

Spider-venom peptides (proteins) have been found to correct the ion channel mutations that underlie many genetic epilepsies.

In Australia, approximately 250,000 people are currently living with epilepsy, with around 3% of the population expected to experience epilepsy at some point in their life.

At present, more than 30% of patients with epilepsy are resistant to treatment and this has not changed in 30 years, despite more than 25 anti-seizure medications on the market. The treatments currently available are aimed at reducing seizure but do not target the specific cause and are often limited by side-effects.

The cutting-edge research is investigating whether spider-venom peptides can help Developmental and Epileptic Encephalopathies (DEEs), severe epilepsies with drug resistant seizures and developmental slowing or regression.

Preclinical testing is underway in the project that aims to prove the safety and efficacy of venom-based drugs by testing them on brain and heart organoids grown at UQ’s Australian Institute for Bioengineering and Nanotechnology from the cells of epilepsy patients.

RBWH Neurologist and University of Queensland Brain, Neurology and Mental Health Theme Lead A/Professor Lata Vadlamudi said the research represents hope for people with these severe epilepsies.

“Epilepsy is a common and severe brain disorder, characterised by seizures. For Developmental and Epileptic Encephalopathies, the seizures represent only the tip of the iceberg in terms of quality of life and below the surface lies intellectual challenges, behavioural issues, gastrointestinal and sleep issues, movement disorders and most devastatingly, increased risk of premature death,” A/Professor Vadlamudi said.

“This leads to an enormous stress on carers looking after their child with a Developmental and Epileptic Encephalopathy.

“Our research stems from observing the long and tumultuous journey that many patients have endured from a trial-and-error approach to anti-seizure treatment.

“We want to change this paradigm, so we can improve quality of life for patients with epilepsy. With innovative patient-specific therapeutics such as spider-venom peptides, we now have the potential for targeted treatment approaches that treat the specific cause and not just the seizure.

“This will be particularly beneficial for patients with genetic epilepsies, for whom current medications do not specifically target the underlying genetic abnormalities.”

UQ Professor Glenn King said that because there are many different types of epilepsy, there needs to be a personalised approach to medication.

“We needed to find compounds that will modulate ion channels in the right way,” Professor King said.

“It turns out that spiders have spent about 400 million years developing very selective and potent modulators of the ion channels that we’re interested in.

“We interrogate those venoms to find small proteins called peptides that will modulate the ion channel in the way we want so we restore normal brain activity in epilepsy patients.”

For people living with epilepsy like Chris De Rooy and her 22-year-old son Seth, who lives with a mutation in the ion channel KCNH1, knowing there is research underway that could help other people like them live a more normal life is incredibly exciting.

“Seth has had epilepsy since he was two years old, and by the time he was 12 he was having up to 48 seizures every year. A lot the time he would end up in hospital because we couldn’t get him to breath. It was very frightening,” Chris said.

“To know there is research happening right on our doorstep that could change the lives of someone like Seth down the track is so heartening.”