Brain Matters Summer 2024–25

Brain Matters

Neuroscience and mental health advancements from The Florey Summer 2024/25

To the moon and back The Melbourne father cycling for his son with epilepsy (pictured)

Family connections The diagnoses driving the next generation of Florey dementia researchers

‘Addiction is not a choice’ Why we need to recognise addiction as a medical condition

Printed on 100% recycled paper

Director’s Update I’m thrilled to bring you the first edition of Brain Matters for 2025, sharing a selection of our most inspiring stories and research insights from The Florey.

It was a big end to 2024 with an Institute-wide scientific review, bringing together internationally renowned experts to assess the strength and impact of research at The Florey. The panel was deeply impressed with the quality of our science, reaffirming our strengths while identifying opportunities for renewed focus. These insights will shape a new strategic plan for The Florey in the coming months,

ensuring we remain at the forefront of neuroscience and mental health research.

Over the festive period we were deeply moved by the incredible efforts of Melbourne father Stu Place, who cycled for 50 days to raise funds for Florey research into SLC6A1 disorder, the rare and life-threatening epilepsy his son Will was born with.

We held a successful summer fundraising campaign to support dementia research, a key priority for The Florey. Many thanks to our donors for your generosity. This support enables Florey discovery science, such as finding that monocytes, a type of white blood cell, appear to clear harmful amyloid-beta plaques

from the brain. This discovery may open some fascinating therapeutic possibilities for Alzheimer’s disease (see page 5 for more).

As we look ahead to 2025, we are excited to build on this momentum, pushing the boundaries of discovery and translational neuroscience. I hope that you enjoy this edition of Brain Matters.

Professor Peter van Wijngaarden Executive Director & CEO

FeBI project to transform blood tests for iron disorders A new technology that uses quantum sensors to better diagnose and manage iron disorders is moving to its next phase, thanks to funding from Australia’s Economic Accelerator (AEA) – a new Government research funding program.

In Australia, around 1 in 5 women and 1 in 20 men suffer from iron deficiency, but many don’t know it because current blood tests are inaccurate and outdated.

Iron deficiency can cause fatigue, poor concentration, weakened immune systems, lower sports performance, complications during pregnancy, and, if left untreated, serious anemia that can be lifethreatening.

Doctors primarily rely on tests that measure ferritin, a protein that stores iron in the body. But these tests aren’t always accurate.

The Florey’s Associate Professor Gawain McColl explains that the new technology, called FeBI (Ferritin Bound Iron), uses advanced diamondbased sensors to directly measure

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the iron inside ferritin by detecting the magnetic fields produced by iron atoms.

FeBI technology is much more accurate than current tests because it can tell whether ferritin contains iron or not. This is important because conditions like diabetes or obesity can increase ferritin levels without increasing the amount of iron, leading to inaccurate test results. As a result, many people with iron deficiencies go undiagnosed.

“Inaccurate test results often mean patients have to go through more tests, which delays treatment and can make it harder for doctors to make the right decisions,” said Associate Professor McColl. “It also puts unnecessary strain on the healthcare system.”

The new quantum sensors could change all that. With this research grant, the team is working hard to develop a prototype that could be used in labs to test patient samples, leading to better and faster diagnoses, and ultimately improving outcomes for

Associate Professor Gawain McColl

patients and healthcare systems.

This project is a collaboration between researchers at The Florey, University of Melbourne, and CSIRO. Learn more

Cover story

Pedal power to fund epilepsy research Melbourne man Stu Place has recently finished a 50-day virtual cycle-a-thon called ‘A Dad’s Will: To the Moon and Back’ to raise funds for Florey research into SLC6A1 disorder, a rare and life-threatening form of epilepsy that his son Will was born with.

Moon is a town in Oklahoma, and Back is in Texas. In total, from Melbourne to Moon and Back is 15,451km. Stu Place recycled up to 309km per day for 50 days in a row. This extraordinary feat of endurance is matched with a fundraising target of $760,000. These funds will contribute to research that aims to develop a new drug for the SLC6A1 disorder.

“Will started having severe seizures at the age of 18 months and having up to 150 seizures a day.

“We first noticed he was missing his developmental milestones from about 6-8 months. A few weeks later we got the diagnosis of SLC6A1, which affects about one in 38,000 births,” Stu said.

Florey researcher, Dr Brett Bennetts, says when the SLC6A1 gene is doing its job properly, it helps maintain balance and calm in the brain.

“Everybody has two copies of SLC6A1 and very rarely, a child is born with a mutation that affects the

function of one copy, leading to a form of childhood epilepsy, known as SLC6A1-Developmental Epileptic Encephalopathy (DEE).

“Children with this condition have severe developmental delays, they have seizures that are difficult to control, and they have a risk of SUDEP – sudden unexpected death in epilepsy.”

For Stu, the heightened risk of SUDEP is the scariest aspect of SLC6A1.

“There’s always a chance of suddenly losing our son. So, the earlier we can attack this disease with a treatment, the better the future will look for Will and others with his condition.”

When Mr Place learned that Florey researchers, led by Professor Steve Petrou, are world leaders in developing mRNA-based precision medicines for childhood epilepsy, he swung into action.

A group of therapeutics called antisense oligonucleotides (ASOs) may help to ease symptoms of the disease by taking advantage of the normal genetic processes that regulate SLC6A1. The goal is to boost expression of the functional copy of the gene, restoring balance in the brain.

“Development of a treatment for SLC6A1-DEE falls under a wider program of research that Professor Petrou has built for the discovery of ASO therapeutics for severe childhood

Stu Place and his son Will

epilepsy over many years,” said Dr Bennetts.

“The efforts of Professor Petrou and his team’s work in this field has already led to successful trials of these types of therapies in severely ill children. Our work with SLC6A1 has potential to deliver precision medicine for Will and other children with this disease, in the near future.”

The cycle-a-thon started on 1 December, with Mr Place chalking up hundreds of kilometres every day, alongside a full-time job and family life. On weekends in his Melbourne CBD site, supporters have been riding alongside Stu, including our Executive Director Professor Peter van Wijngaarden, Florey epilepsy researchers and support staff.

“People have come in off the street to donate. An absolute stranger came in and gave $500. It’s complete generosity.

“Every dollar raised goes towards The Florey finding a treatment, and we hope that our efforts will get that treatment to clinical trial,” Mr Place said.

Professor Nadia Rosenthal at The Florey In a stand-out moment for scientists last November, The Florey hosted Professor Nadia Rosenthal, a world leader in regenerative medicine, to deliver the 2024 Allan and Maria Myers Lecture.

Hailing from Maine, US, Professor Rosenthal is the Scientific Director at The Jackson Laboratory.

Professor Rosenthal shared insights into the possibilities of creating experimental models that more accurately reflect the complex genetic diversity of humans.

Watch the lecture

Brain Matters Summer 2024/25

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The inspiration driving the next generation of dementia researchers Florey PhD students Patricia Wongsodirdjo and Thomas Nguyen became interested in studying Alzheimer’s disease when they experienced the impact of dementia on their family members.

Working in the Dementia Mission of The Florey, their research is investigating early prevention strategies and new treatments for dementia.

Their personal stories are featured as part of The Florey’s More Time fundraising campaign, which is dedicated to advancing critical research to give people with dementia more time with their loved ones.

Patricia Wongsodirdjo always knew she wanted to study dementia drug development.

Working under the supervision of Dr Rebecca Nisbet and Dr Laura Vella, Patricia has now been studying Alzheimer’s disease for the past 3 years.

“The main reason I wanted to pursue research, especially in the development of Alzheimer’s therapeutics, was driven by my frustration with the ineffective treatments given to my great aunt and grandma.”

Patricia’s family became caregivers of her great aunt when Patricia was still in high school.

“It was especially difficult for us,” she said. “We took her to see doctors, but the best treatment available at the time was mostly supportive, and didn’t improve her condition.”

Patricia’s great aunt passed away in 2019 after battling the disease.

Today, Patricia’s family takes care of her grandmother, who is living with dementia.

“My grandma is in her 80s, so you might expect some memory loss at that stage. But the memory loss we observed was just exponential.”

Patricia said her grandmother’s condition became ‘really, really pronounced’ after she lost her sister, Patricia’s great aunt.

“It was challenging for me to see how this disease reduced her personality. It’s a devastating disease both for the patient as well as the caregivers.”

Thomas Nguyen was also motivated by his grandmother’s diagnosis.

PhD student Thomas Nguyen

“The research question that I am trying to answer is how neurons in the brain are dying in dementia,” Thomas said.

Thomas’ great passion for neuroscience stems from wanting to study the universe, almost the way astronomers do.

“As a neuroscientist in training, I am studying the universe within each of us that is the interconnected network of the neurons in the brain, and I think that’s beautiful.”

Thomas’ grandmother was diagnosed with Alzheimer’s disease when he was in high school. Thomas says the disease transformed his grandmother from someone caring

mRNA hope for Niemann-Pick disease Florey researchers are investigating mRNA treatments for the neurodegenerative condition Niemann-Pick disease Type C. This research is made possible, in part, thanks to funding by the Australian NPC Disease Foundation.

Niemann-Pick disease Type C or NP-C is a form of dementia that causes children and young people to suffer irreversible intellectual decline, loss of motor skills, seizures and eventually death.

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Using an mRNA gene therapy approach, Florey researchers hope to correct the action of the mutation in the gene that causes NP-C. Mandy Whitechurch – mother of Timothy, 35, and Matthew, 37, who both have NP-C – started the Australian NPC Disease Foundation about 15 years ago.

Timothy was diagnosed in 2007 at the age of 18 and Matthew was diagnosed 6 months later.

“The foundation’s work isn’t going

to help my boys,” Ms Whitechurch said. “But it’s going to help somebody else. We’ve got to have hope. We can’t give up on our kids, we’ve got to be their voice.”

Dr Ya Hui Hung is leading The Florey’s work on an mRNA treatment for NP-C and says the project would not have taken off without their initial support.

“Mandy and the foundation supported my idea of pursuing an mRNA gene therapy for NP-C in 2018,

Gobbling up Alzheimer’s plaque

“The main reason I wanted to pursue research, especially in the development of Alzheimer’s therapeutics, was driven by my frustration of the ineffective treatments given to my great aunt and grandma.”

PhD student Patricia-Wongsodirdjo

and fun to a completely different person.

“I witnessed her condition deteriorate so rapidly,” Thomas recalled. “I felt sad, frustrated, scared and hopeless.”

Our next generation of dementia scientists work with a new-found hope.

Patricia highlights the promise of recent advances in dementia therapies. “At the time when we were taking care of my great aunt, there were no disease-modifying treatments in the market yet,” she said. “But now, things are picking up.”

Thomas explained that every 3 seconds, someone somewhere in the world is diagnosed with dementia.

“And what is so mysterious is we don’t have a cure to stop the brain cells from dying.”

before mRNA had been successfully used in COVID vaccines”.

Dr. Ya Hui Hung states there is growing optimism in the search for better and more effective treatments.

“Last year marked an incredible milestone with two new FDA approvals for NP-C treatments.

I’m excited about new gene therapy approaches that target the root cause of the disease – rather than just symptom management. We have promising results in preclinical models that can turn our findings into real treatments.”

“So, I hope that with my research, we can lay a foundation for future researchers to build upon to find a cure for dementia – and I hope one day, instead of 3 seconds, it would be 4 seconds, then 5, then one hour, and then months. That is the hope.”

Help us change the reality of dementia.

Donate to support dementia research:

Florey researchers have made an important discovery: monocytes, a type of mobile white blood cell in our bodies, can help clean up the plaque-causing amyloid-beta protein (Aβ) throughout the body.

Aβ accumulates in the brains of people with Alzheimer’s disease.

Previous research has shown that immune cells that reside in the brain – called microglial – can clean up Aβ. But research from Florey investigator Dr Xin Huang, published in Nature Communications, has shown that monocytes can also perform this role.

The researchers observed that monocytes can migrate from the blood circulation into cerebrospinal fluid, and then back to the circulation and peripheral lymph nodes.

“We found that participants in Australian Imaging Biomarkers and Lifestyle study, who had mild cognitive impairment and Alzheimer’s disease had much lower levels of Aβ on the surface of their blood monocytes compared with people of similar age without cognitive impairment.

This suggests that, in people with Alzheimer’s, less Aβ is being cleared away,” Dr Huang said.

Excitingly, these findings could open new avenues for treatment in Alzheimer’s disease.

“We will continue to explore how to activate monocytes to more effectively gobble up neurotoxic accumulations in the brains of people with Alzheimer’s disease.”

Dr Xin Huang

Dr Ya Hui

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Expansion of stroke registry to improve care The Australian Stroke Clinical Registry (AuSCR) at The Florey is set to expand its work to improve stroke care thanks to new funding from the Australian Government.

Since 2009, AuSCR has collected data of stroke patients from participating hospitals to monitor and improve the quality of acute stroke care.

The AuSCR data custodian, Professor Dominique Cadilhac, said the new agreement recognised the impact the stroke registry was already having on care.

“With the Commonwealth’s support, we will be able to achieve greater coverage across the country.

Our work will extend to smaller hospitals to provide a comprehensive overview of stroke care in Australia, something never previously achieved.”

Professor Cadilhac said stroke is a major cause of disease burden and health care cost.

“Every 19 minutes, somebody experiences their first stroke, with those in regional areas 17% more

likely to suffer a stroke than those in metropolitan areas. We know that smaller regional hospitals stand to benefit from our monitoring of their acute stroke care, and we look forward to working closely with them.”

This new funding enables the AuSCR to: • Expand the number of interactive data dashboards to support care improvements • Make up-to-date information more accessible to the public and researchers • Share knowledge and expertise with more hospitals • Report outcomes based on factors such as sex, ethnicity, and stroke type.

The AuSCR team

“Whether a person recovers well from stroke or has a lengthy rehabilitation can depend on the hospital where they’re treated. We are working to change that, by improving the gathering and sharing of information so that all patients can get access to the highest standards of care,” she said.

Stroke has been identified as one of Australia’s high-priority clinical domains. All hospitals already working with AuSCR support the National Stroke Targets which were established in 2023 with the Stroke Foundation, New Zealand Stroke Organisation and others.

Professor Cadilhac said for Australia to align with international best practice it was essential that all hospitals have access to AuSCR’s data infrastructure as it monitored their progress against National Stroke Targets.

Promising research for obsessive-compulsive disorder Early research at The Florey suggests the psychedelic compound, psilocybin, has potential to treat obsessive-compulsive disorder (OCD) and related disorders.

OCD is a mental health condition that affects an estimated 3.1% of adults in Australia every year. Like many mental health conditions, treatment options are limited.

The study – led by Florey PhD student James Gattuso and supervised by Dr Thibault Renoir and Professor Anthony Hannan – found a single dose of psilocybin may reduce compulsive behaviours in mice.

Mr Gattuso worked with mice that are recognised as ideal for studying repetitive behaviours due to their

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compulsive grooming behaviour.

The animals, called SAPAP3 knockout (KO) mice, groomed themselves much less after a dose of psilocybin, suggesting a decrease in compulsive tendencies.

In their paper, published in the journal Neuropharmacology, the team describe how psilocybin also increased physical activity in the control mice but not in the OCD model mice.

“This indicates that the OCD mice have altered serotonin functionality compared to control mice. Serotonin is an important chemical messenger in the brain. Serotonin receptors are linked to compulsive behaviours and so it is possible that psilocybin

corrected the altered serotonin functionality in KO mice. This theory needs to be tested in follow up molecular experiments,” Mr Gattuso said.

The lead author, Dr Thibault Renoir says, “Current treatments, such as selective serotonin reuptake inhibitors (SSRIs), require prolonged use, often have side effects, and leave some patients without adequate symptom relief.”

Psilocybin’s rapid and enduring effects, which lasted up to a week following the psilocybin injection, make it an exciting candidate for further research and potential therapeutic applications in OCD and related conditions.

“More than 100 million people globally have an alcohol use disorder. Yet most receive no treatment.”

Professor Andrew Lawrence

Treat addiction as a medical condition, not a personal choice

by Professor Andrew Lawrence I undertook my PhD in the 1980s, studying opioids and opioid receptors. Back then I figured I would rather study ‘pleasure’ than ‘pain’, although the two are often linked.

I now understand the enormous scale of the problem that is addiction.

More than 100 million people globally have an alcohol use disorder.

Yet most receive no treatment.

This is partly because of a historic lack of understanding that addiction is a medical condition, not a personal choice.

Alcohol misuse is among the world’s leading causes of illness and death, and although evidence suggests it can be treated, many don’t seek – or receive – help.

The impact of any individual’s addiction can be far-reaching, causing harm to themselves plus others in their orbit, the economy and social fabric of our society. It likely affects us all in one way or another.

Experimenting with drugs or alcohol is not unusual and isn’t limited to ‘weak’ or ‘bad’ people.

Evidence suggests that drug and alcohol misuse can lead to adaptations in the brain at a cellular level that underpin the addicted state. This helps to explain why people respond to

drugs and alcohol differently.

We need more targeted treatments that engage and counter these drug-induced brain adaptations.

Personality, cognitive ability, psychiatric conditions and social factors are part of a constellation of ‘enablers’ interacting with a myriad of outcomes.

Large longitudinal studies are aiding our understanding of drug and alcohol use disorder.

New technologies and laboratory research are starting to show us how alcohol and drugs impact brain cells with unprecedented detail.

At The Florey, we are studying alcohol-induced adaptations in human and rodent brains with the aim of finding potential new treatments.

We’re also learning about sex differences and alcohol’s impact on the brain and the notion that there’s likely a need for gender-specific treatments.

All these approaches have the potential to uncover – and result in – a range of new treatments and interventions.

It’s time we recognise addiction as a medical condition worthy of treatment and research – not a personal choice.

Want to hear more from Professor Andrew Lawrence on addiction?

Listen to The Florey’s new Brain Matters Podcast and join researchers, clinicians and those with lived experience as they tackle some of the biggest challenges in neuroscience.

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Mother’s bequest in her son’s memory Sally Beavis has faced many hardships in life. It’s this experience of adversity that helps her understand the need for mental health.

Sally was 36 when she experienced late onset schizophrenia, however her son Quentin was 20 when his own battles with the mental health condition began. Tragically, his mental health deteriorated, and at 24 he took his own life.

His death left Sally devasted and in disbelief, resulting in her joining a bereavement group with other parents who experienced a similar tragedy.

“After such a catastrophe, it is human nature to do all you can do to prevent others from suffering the

same fate,” she said.

Sally realised there wasn’t enough known about schizophrenia, and her research led her to The Florey.

She connected with Associate Professor Jess Nithianantharajah, a leading mental health researcher at The Florey who told her about research on a potential treatment for medication-resistant schizophrenia.

Sally has decided to include a gift in her Will to support The Florey’s brain research.

“I am proud that my bequest will continue this vital research and encourage others to help end this scourge. Too many sons and daughters have been lost forever and parents, families and friends left permanently

Sally Beavis with her son Quentin

broken-hearted,” Sally said.

If you require immediate support or mental health advice, please call Lifeline on 13 11 14.

Full house for dementia public lecture

Panel: Associate Professor Nawaf Yassi, Dr Rebecca Nisbet and Professor Scott Ayton

Last October, The Florey gathered a full house for our public lecture on the diagnosis and treatment in a new era for dementia, highlighting exciting advances in dementia research.

Experts shared insights into current and emerging treatments for Alzheimer’s disease, the critical role of quick and accessible diagnostic tools and new research techniques that hold promise for the future of dementia care.

Watch on our YouTube channel

The Florey Society’s annual lunch The 2024 Florey Society lunch was attended by an enthusiastic group of The Florey’s Gift in Will supporters.

The Florey’s Executive Director & CEO, Professor Peter van Wijngaarden, hosted the event, and Professor Chris Reid, Florey’s Epilepsy Mission Lead, delivered a talk about his team’s groundbreaking work treating rare childhood epilepsy.

If you have included The Florey in your Will, we invite you to join The Florey Society.

For more information, please contact Nola Wilmot on 03 9035 9710 or nola.wilmot@florey.edu.au

Guests at The Florey Society’s annual lunch

Acknowledgement of Country The Florey acknowledges the Traditional Owners of the land on which we work, the Wurundjeri people of the Kulin Nation. We pay our respects to their Elders past, present and emerging. The Florey is committed to the aims, principles and actions of marra ngarrgoo, marra goori: The Victorian Aboriginal Health, Medical and Wellbeing Research Accord.

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