Kindie Kastrissios keeps a bag packed at her front door ready for the next emergency visit to hospital with daughter Scarlett.
Scarlett Mayfield-Smith will not turn three until March next year, but she’s already had more than 50 ambulance rides to hospital after developing seizures as a baby.
Some of her seizures have lasted for hours, rather than minutes.
Scarlett developed seizures as a baby. (Supplied: Kindie Kastrissios)
The Brisbane toddler has been on a merry-go-round of trialling different anti-seizure medications to find an effective combination without debilitating side effects, such as sleepiness, behavioural issues, and loss of appetite.
“I think we went through eight medications to get to where we are now — failing mostly,” her mum said.
“It’s just all a guessing game.”
Scarlett has trialled many medications, some with alarming side effects. (Supplied: Kindie Kastrissios)
One drug resulted in her “banging her head against the wall”, another caused her to fall “asleep in her hands” at the dinner table. She also lost weight on a different drug and her epilepsy worsened on another tablet.
“The medication just knocks them around so much,” Ms Kastrissios said.
Scarlett has had three convulsive seizures – known medically as tonic clonic seizures – this year.
She’s one of about 30 per cent of people with epilepsy whose condition is considered refractory – when medication fails to bring the seizures under control. The cause of her epilepsy remains unknown.
Some of Scarlett’s seizures have lasted several hours. (Supplied: Kindie Kastrissios)
Her mum said Scarlett’s condition had improved this year on a new drug regimen.
But her big hope is that future research will result in much better epilepsy drugs to allow her daughter and others like her to live a relatively normal life free of seizures, which can be life threatening.
Ms Kastrissios has welcomed the federal government’s Medical Research Future Fund giving $4.1 million to University of Queensland (UQ) researchers to test spider venom proteins as potential epilepsy drugs.
Spider venom potential
Venom researcher Glenn King of UQ’s Institute for Molecular Bioscience said the four-year study would test spider venom molecules against brain tissue made from the blood of individual epilepsy patients.
Professor Glenn King has been working on venom-based drugs for epilepsy since 2017. (Supplied)
Scientist Selin Pars, of UQ’s Australian Institute for Bioengineering and Nanotechnology, is taking the blood of patients with epilepsy, isolating the white blood cells and reprogramming them to form stem cells that can be turned into most cell types in the human body – including brain cells.
Dr Pars, who works with the study’s leader Professor Ernst Wolvetang at UQ, can then create functional brain tissue, dubbed brain “organoids”.
She said the lentil-sized organoids contained the key cell types of the human cortex – the outermost layer of the brain – mostly neurons and glia.
Dr Selin Pars said the brain organoids would be ready to test spider venom peptides from early 2025. (Supplied)
The post-doctoral researcher will create 800 organoids for the research. The process takes about seven months from when the blood sample is collected from an epilepsy patient.
Dr Pars said brain organoids would be ready to test spider venom peptides from early next year.
Preliminary research testing of a peptide found in the venom of a large west African tarantula, known scientifically as Heteroscodra maculata, shows it reduces the firing of neurons in brain tissue derived from the blood of children with specific types of genetic epilepsy.
Tests using venom from a large west African tarantula had promising results. (Supplied: Bastian Rast)
The latest study will test venom molecules on brain organoids created from the blood of children with different forms of epilepsy, including a severe and life-long drug-resistant epilepsy, known as Dravet syndrome.
Dravet syndrome is caused by variants in the SCN1A gene, affecting a protein important for the brain’s electrical activity.
“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,” Dr Pars said.
“We need therapies … to be more specific. It’s a great example using this research to see how this can be achievable and hopefully can be brought into clinical trials and potentially as a treatment, if everything goes well.”
Professor King is a venom researcher at UQ’s Institute for Molecular Bioscience. (Supplied)
Professor King has been working on venom-based drugs for epilepsy since 2017.
He said 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,” Professor King said.
He said his team would also screen for other venom molecules that may help treat different genetic epilepsies.
Professor King’s team will also explore other venom molecules in their quest to treat epilepsy. (Supplied)
For example, as part of the new research, the scientists will test venom molecules on brain organoids created from the blood of people with seizures caused by mutations in the KCNH1 and KCNQ2 genes.
The KCNH1 gene was first linked to severe epilepsy by Brisbane researchers 10 years ago.
“All the epilepsies we work on are genetic epilepsies,” Professor King said.
“People think of epilepsy as being a single disease, but it’s not.
“It’s a lot of different things and so we want to be more specific in terms of the treatment that we’re developing for patients.
“We’re trying to develop personalised medications that we know will work for particular groups of epilepsy patients.”
The cause of Scarlett’s seizures is unknown. (Supplied: Kindie Kastrissios)
They have access to venoms from other spiders, as well as from ants, assassin bugs, scorpions and caterpillars.
After years of work in Professor King’s laboratory, a molecule found in the venom of a K’gari funnel web spider will soon move into human trials as a treatment to prevent heart damage during a heart attack.
More research needed
While the epilepsy research is also promising, Professor King said even if venom-derived drugs proved safe and effective, much more work was needed before they reached patients with seizures.
He said the drugs could not be given orally.
“It would have to be injectable or there would have to be an implantable device that delivered it to the brain, most likely,” Professor King said.
“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.'”
University of Sydney medicinal chemist Michael Kassiou, who is not involved in the venom research, described drug discovery using organoids as an exciting emerging area in science.
He said organoids were better than animals at testing the potential effectiveness of an experimental drug as a treatment for human disease.
“Obtaining a favourable 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.
“It will enable us to make better decisions as to what we think is clinically relevant and what is not.”
Brain tissue for the study is made from epilepsy patients’ blood. (Supplied)
Professor Kassiou, who is the head of the NSW Organoid Innovation Centre, said that did not mean animals had no place in drug discovery research.
“But you can’t just solely depend on the behavioural response of an animal model to then say this is going to work in a human,” he said.
“I keep telling people ‘Humans don’t make good models for rodent disease’. You need to be thinking about models that actually model the disease that you’re going to treat, and organoids are much better at doing that.”
Professor Kassiou, who also leads the University of Sydney’s Centre for Drug Discovery Innovation, said there was a huge unmet need for drugs to treat brain disorders, including epilepsy.
Hope for epilepsy patients
Epilepsy Queensland’s interim CEO Sandi Rodiger said just knowing “things are happening in the research space for epilepsy, ultimately gives people hope” for more effective treatments, particularly for patients with refractory epilepsy and their families.
Sandi Rodiger says people with epilepsy still experience stigma. (Supplied)
Ms Rodiger said the impact of epilepsy for individuals could be huge, including the risk of physical injury during a seizure, memory problems, and significant loss of independence.
Many were disqualified from driving.
She said more than half of people with epilepsy experienced anxiety and depression.
“People who live with refractory epilepsy, it can be quite devastating, and it can be catastrophic,” Ms Rodiger said.
She said stigma in the community associated with epilepsy was still high.
“We talk to clients who contact us and tell us that they experienced a seizure in a public place, and nobody comes to their aid because they’re assumed to be drug or alcohol affected,” Ms Rodiger said.
“Often people don’t disclose their epilepsy because they’re worried about the reactions.”
Scarlett’s favourite place is the beach. The toddler is one of 250,000 Australians living with epilepsy. (Supplied)
Epilepsy Action Australia estimates that more than 250,000 Australians live with epilepsy.
Scarlett Mayfield-Smith’s epilepsy affects the whole family.
The two-year-old still sleeps in her parents’ bed just in case she has a seizure.
Scarlett, pictured here with her sister Lillie and cousin Tommie, turns three next year. (Supplied: Kindie Kastrissios)
Mum Kindie Kastrissios was unable to attend her grandmother’s funeral because Scarlett was in hospital and had a seizure before the service.
Scarlett’s nine-year-old sister Lillie has also had to forego gymnastics lessons and other activities because of her sister’s seizures.
“It’s just a constant unknown,” Ms Kastrissios said.
“You don’t know when it’s going to happen or where.”
But she’s heartened by research happening in her own backyard that may lead to a new class of epilepsy drugs in her daughter’s lifetime.
“It excites me to know that there could be something on the horizon,” Ms Kastrissios said.
