Brain Matters Spring 2025

Brain Matters

Neuroscience and mental health advancements from The Florey Spring 2025

Making a global difference in NYC for lived experience consumers Page 4

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Director’s update As we welcome Spring, I hope you enjoy the latest edition of Brain Matters, which showcases the remarkable breadth of our work at The Florey.

In this issue, we explore advancements in Parkinson’s disease research, including a promising treatment developed at The Florey to cloak human neural grafts and help them evade immune detection. We also learn about the development of precision medicines to treat a rare neurodegenerative disease.

On our front cover, we highlight the work of Brooke Parsons, a Consumer Consultant with our stroke team, whose passionate advocacy is

helping to ensure that people with lived experience of neurological conditions are central to the research that shapes their care.

I would also like to extend a heartfelt thank you to our donors who contributed to our tax appeal in support of dementia research. Your generosity is directly driving scientific discovery and making a tangible difference in the lives of many.

This impact is brought to life in this edition through the stories of our supporters and the researchers they empower. We’re proud to highlight Tania West, who is supporting the work of Dr Carlos Ganter in investigating ways to reverse earlystage neurodegeneration in honour

of her late father who battled multiple system atrophy (MSA), and the enduring legacy of the late Harold Mitchell AC, whose support is enabling Dr Emily Ramage to drive research into young stroke on a global scale.

Thank you for your continued support of The Florey.

Professor Peter van Wijngaarden CEO and Executive Director of The Florey

Next-gen precision therapies to treat rare genetic disease Dr Dmitry Ovchinnikov, a molecular geneticist and stem cell biologist at The Florey, has been awarded funding to validate novel precision medicines to treat a rare disease in children, ataxiatelangiectasia (A-T).

A-T is an incurable and fatal form of progressive neurodegeneration diagnosed in children. It affects their movement, speech and coordination, leading to severe disability and premature death. The disease also affects the immune system, placing children at higher risk of chest and lung infections, and increases their risk of developing various cancers.

Dr Ovchinnikov’s grant, from US-based foundation A-T Children’s Project and Brisbane-based BrAshA-T, will support his research into developing techniques to increase the production and activity of the ATM gene – one of the genes that is deficient or missing in children with the disease.

The ATM protein, which is encoded by the ATM gene, is a double-edged sword. It performs multiple functions in

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Brain Matters Spring 2025

many cells in our bodies. Too little ATM leads to ataxia, while too much could also pose some risks.

But ATM is also like a Swiss army knife, he says.

“It is one of the biggest proteins in the body that does many things in many cell types. As such, it comes with inbuilt ‘brakes’ limiting its expression. Removing the brakes allows us to achieve the desired boost by harnessing existing natural mechanisms.”

Dr Ovchinnikov says treatments like cell replacement therapy, which are currently being trialled for epilepsies or Parkinson’s disease, are not suitable for tackling A-T, due to the elaborate architecture of this brain region that is most affected in the disease.

However, antisense oglionucleotides (ASOs), which offer an increase in protein expression or mRNA levels, the development of which has been pioneered at the Florey by Professor Steve Petrou, may be a practical solution.

He believes the team can use their understanding of the ATM gene’s biology to boost remaining ATM in many

Dr Dmitry Ovchinnikov

A-T patients and ultimately, restore the gene’s function to sufficient levels.

Dr Ovchinnikov thanked A-T Children’s Project and BrAshA-T for their support of his research, which has also been made possible through the generous support of the Live Life Foundation.

“I am grateful for the international support of this project,” he said. “We hope to translate our understanding of the biology of the gene affected in this debilitating ataxia to develop effective and precise molecular therapies, with our approach designed to benefit many children affected by this disease around the world.”

A daughter’s love and a dad’s legacy Supporting Florey research into multiple system atrophy For Tania West, losing her beloved Dad, Graham, to a rare form of Parkinson’s disease, was a heartbreaking experience.

Graham lived a rich and full life in Canberra as a husband, father and grandfather, and was a highly respected automotive trade teacher, before succumbing to multiple system atrophy (MSA), a rare, progressive neurological condition.

“Dad taught us to show kindness, empathy, hard work, gratitude, to live life with joy and positivity, to have good manners and show love. He could fix anything, was gentle and had a heart of gold. He was – and still is – my hero. We love and miss him beyond words,” says Tania, who also lives in Canberra.

MSA causes brain cell loss and is a form of atypical Parkinson’s or “Parkinson’s Plus” diseases.

These diseases have Parkinson’slike symptoms – such as tremors, rigidity and autonomic dysfunction – but don’t typically respond well to dopamine replacement treatment.

Tania West with her late father Graham

Sadly, Graham died in 2022. Still deep in their grief, his family has decided to honour him by establishing The Graham West Research Grant to support Dr Carlos Gantner’s research at The Florey.

“This will form part of Dad’s legacy,” Tania says. “We wanted to fund a specific project or program that focused on Parkinson’s Plus and associated MSA. I contacted The Florey’s Philanthropy Manager, Ryan McCarthy, who suggested a project looking at the connection between sleep dysfunction and early detection of Parkinson’s disease and MSA. Given that my dad was diagnosed so late, I felt this was something quite personal to our story.”

In hindsight, Tania realises her father may have been exhibiting symptoms for 8 years before his diagnosis in 2019. By then he had already been admitted to hospital 28 times after numerous seizures, issues with stability and balance, headaches and speech problems, as well as countless tests and reviews.

After diagnosis, the family learned that he would likely decline rapidly.

“It was very hard to watch. No treatments helped. My beautiful Mum, Jenny, was able to take care of him at home for a while, but as the disease progressed it became harder to manage.”

They made the heartbreaking decision to move Graham into residential care.

“It was so hard to watch my proud Dad deteriorate, needing help with toileting, eating and communicating.

This would have been so hard to go through, but he never once complained. Even on tough days he’d say he was ‘feeling fair’.”

Graham was just 70 when he passed away.

“Dad was an incredible man who left us way too soon. I hope that by funding research at The Florey, we’ll be saving and improving the lives of

Dr Carlos Gantner with Tania West

people living with Parkinson’s disease and MSA.” The Graham West Research Grant is supporting Dr Carlos Gantner’s research into the brain circuitry, brain cell types and degeneration that occurs in REM sleep behaviour disorder.

Carlos says MSA – like Parkinson’s disease and dementia with Lewy bodies – is often preceded by sleep problems, in particular REM sleep behaviour disorder, where patients act out their dreams.

“My goal is to develop effective strategies to reverse degeneration at the earliest stages, before a person progresses to Parkinson’s disease, MSA or dementia with Lewy bodies,” he says.

“Once we understand why people transition to the disease, we can potentially unlock targeted treatment strategies for each disease. Tania’s generous donation is an incredibly important support for our research, and we’re determined to put it to good use investigating – and improving – treatment options for people like Graham.”

Tania is excited to contribute to medical research.

“It could be groundbreaking,” she says. “We need better ways of preventing, screening and treating this disease. And we want a cure! We need to be able to provide a better quality of life and improve life expectancy for people with Parkinson’s and MSA. What a wonderful way to honour my amazing Dad.” To discuss ways you can support vital research at The Florey contact Ryan McCarthy: ryan.mccarthy@florey.edu.au

Brain Matters Spring 2025

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Cover story

Accessibility in New York: A Q&A with Brooke Parsons

Brooke Parsons is a lived experience consumer consultant for stroke projects at The Florey.

In June she travelled to New York to attend the 18th Conference of States Parties (COSP18) to the Convention on the Rights of Persons with Disabilities, as a Stroke Foundation Future Leaders Grant recipient.

We sat down with her to reflect on her time in New York and her work advocating for people with lived experience in research.

Q: What did you do at the UN? At the UN while attending COSP18, I took part in important discussions about how to improve the lives and rights of people with disabilities worldwide. I listened to presentations, joined roundtable sessions and contributed my insights, especially about making sure people with disabilities are included in decisions that affect them.

I learned about key topics like using new technology to support inclusion, innovative ways of funding 4

Brain Matters Spring 2025

disability programs, and ensuring the rights of groups who often face extra barriers, like Indigenous people with disabilities. I also connected with other advocates, policymakers and experts from around the world, helping to build networks and share ideas for stronger disability inclusion.

Q: You visited several hospitals while in New York. What did you learn about the role of lived experience in those institutions?

During my visits to several hospitals in New York – including New York Presbyterian Hospital, Burke Neurological Rehabilitation Institute, and the Lennox Hill Stroke Unit – I learned that lived experience plays an increasingly important role in shaping care and services.

I learned that we in Australia are further along the path of including lived experience in our research and that New York is willing and wanting to learn from us.

Staff and leaders in these institutions recognise that people who have personally experienced stroke, disability, or neurological

conditions bring valuable insights into how care can be more patientcentered, respectful, and effective.

They shared how they could involve people with lived experience in areas like program design, research, and support services.

Q: As somebody who has survived a stroke and now uses a wheelchair, did you experience any accessibility issues on your trip?

Yes, I experienced some accessibility challenges during my trip to New York. While many places – like the UN buildings and major hospitals – were quite accessible overall, there were still barriers in public spaces, transportation, and older buildings.

Some sidewalks were uneven or crowded, making navigation difficult. Certain restaurants, shops, or attractions had steps or narrow doorways without ramps. Public transportation, though improving, sometimes involved stations without working elevators, or confusing signage.

Despite these issues, I also noticed positive efforts toward accessibility

“The fellowship has been instrumental in helping me shape my research path.”

Dr Emily Ramage

Travel fellowship powering global young stroke research Dr Emily Ramage, a Senior Research Officer working within the Florey Stroke team, is at the forefront of a growing effort to understand and address stroke in young adults.

in many parts of the city, including accessible hotel rooms, some newer public facilities, and staff who were often willing to help.

My experiences reinforced the reality that while progress has been made, there’s still significant work needed to ensure full and seamless access for people with mobility challenges, both in New York and worldwide.

Q: Where to next?

After my inspiring trip to New York, my journey continues both personally and professionally. I’m looking forward to sharing what I’ve learned at COSP18 and from the hospital visits, using those insights to strengthen my advocacy and work for people with disabilities.

Wherever I go next, my mission remains clear: to help create a world that’s more inclusive, accessible, and informed by the voices of people with lived experience.

I’m grateful beyond words to have travelled to New York with funding from the Stroke Foundation Future Leaders Grant and the Florey Institute.

In 2024, she was awarded the Harold Mitchell Postdoctoral Travel Fellowship, a travel award funded by the Harold Mitchell Foundation to help further the careers of postgraduate students and postdoctoral researchers at The Florey.

The award enabled her to travel to Europe in May 2025 to present her work on the Young Stroke Deep Phenotyping Project, and the Global Young Adult Stroke Research Alliance at two major international events: the International Stroke Genomics Consortium in Sweden and the European Stroke Organisation Conference in Helsinki.

Dr Ramage’s work aims to bridge the gap in research on why strokes occur in young people and how to support better outcomes for their care.

Concerningly, stroke rates are rising among young adults – and in one in eight cases, the cause remains undetermined.

Even when the cause is known, there is a lack of strong evidence to guide young stroke survivors toward effective treatment and secondary prevention.

While in Helsinki, Dr Ramage co-led the inaugural in-person meeting of the Global Young Adult Stroke Research Alliance with the

Florey’s Professor Vincent Thijs. The alliance was formed in January 2025 and has brought together up to 50 members from across the globe. These include a mix of health professionals, scientists and people with lived experience of stroke. This meeting touched on the important priorities of the alliance to maximise impact in young adult stroke research.

Dr Ramage says the alliance aims to optimise the relevance, quality, and support for research in young stroke through positive collaboration and building the capacity and capability of researchers in the field.

“We hope to accelerate research in young stroke to improve the diagnosis, prevention, management, and life after stroke by tackling important research areas on an international scale.”

The alliance is now working to kickstart their priority actions, expand its network of partner organisations, and secure additional funding.

Dr Ramage says the fellowship has enabled her to engage with a diverse international community, which has enriched the quality of her research and also broadened its global significance.

“The fellowship has been instrumental in helping me shape my research path and establish long-standing networks during this pivotal stage of my career. I would like to express my sincere thanks to the Harold Mitchell Foundation for this opportunity.”

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Innovations in Parkinson’s disease What is Parkinson’s disease?

Parkinson’s disease is a progressive neurodegenerative disorder that affects an estimated 10 million people globally and 150,000 people in Australia.

This disease causes significant impact on motor function in patients, which includes tremors, painful muscle contractions and other impairments. The motor dysfunction seen in Parkinson’s disease is caused by the loss of a single cell type in the brain, called the dopamine neuron which normally produce dopamine that is necessary for controlling movement.

Current drug treatments focus on the replacement of dopamine in the brain. While they do provide significant benefit to patients, their long-term use is hindered by a loss of efficacy – their benefits do not last over time because as the disease gets worse, the replacement of dopamine is no longer enough to compensate.

Cell replacement therapies At the Florey, Dr Niamh Moriarty is working on dopamine cell replacement strategies to restore motor and cognitive function in people who live with Parkinson’s disease.

Cell replacement therapy involves generating new and healthy dopamine neurons, which are then transplanted into the brains of Parkinson’s disease patients (a process

Dr Niamh Moriarty

known as neural grafting) to replace the neurons that were lost to the disease.

We generate these healthy dopamine neurons from stem cells.

“I like to think of stem cells as your early, primitive cells.

They have all the potential in the world and haven’t decided what they want to be when they grow up yet,” she says.

They can become one of over 200 cell types. So, by using very defined protocols, scientists can instruct these stem cells to become dopamine neurons.

Dr Moriarty’s research aims to improve the survival of dopamine neurons after transplantation, and their ability to connect with the brain, which all leads to better recovery with motor and non-motor symptoms.

The non-motor symptoms, such as impaired cognition, are just not talked about as much and may be less understood, even though they are in no way less significant.

Harnessing mRNA to prevent and slow Alzheimer’s disease mRNA Victoria has funded 2 Florey projects to prevent and treat Alzheimer’s disease, with the potential to help establish Victoria as a leader in the development of mRNA-based therapies.

Dr Abdel Belaidi

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Brain Matters Spring 2025

Since mRNA vaccines were developed during the COVID-19 pandemic, researchers around the world have been working on ways to harness the potential of this technology to treat neurological conditions.

Florey researchers have engineered a way to fool the immune system into accepting neural grafts as part of the body, rather than attacking them as foreign objects, in a new study published in Cell Stem Cell.

The study’s lead author, Florey Deputy Director Professor Clare Parish, Head of Stem Cells and Neural Development, said neural grafting is an emerging treatment to replace those dead neurons.

“Human neural graft trials are underway overseas but, as with other types of organ or cell transplants, patients need to stop their body rejecting the graft by taking immunosuppressant drugs several times a day.

Unfortunately, these drugs carry their own risks and side-effects.”

Professor Parish said the team, in collaboration with the University of Toronto, has taken neural grafts to the next generation, and the work could benefit other cell transplants.

“We’ve engineered neurons which are like those currently in clinical trials for Parkinson’s disease, but we’ve also given them an invisibility cloak. They can hide in plain sight from the immune system. This could mean an end to the need for anti-rejection drugs.”

The paper’s co-lead author, Dr Chiara Pavan said the team tested the engineered neuronal grafts in mice with a ‘humanised’ immune system, and in rats modelling Parkinson’s disease.

“After receiving their neuronal graft, the mice showed no negative effects – which is a good indication that the human immune system will accept the neurons. In rats, the signs of Parkinson’s disease were abolished, indicating the cloaked neurons don’t lose their effectiveness against the disease,” she said.

Dr Pavan said the neurons also had an ‘off’ switch so that they can be activated if desired, to eliminate the risk of tumours developing from grafts.

Professor Parish said it is an exciting result, and the technology has huge potential.

“We’ve made a cell product that in future could be implanted in people with Parkinson’s disease, reducing the need for anti-rejection drugs,” Professor Parish says “This is the next generation of neurological treatment, and it could be used as a safe, off-the-shelf cell product suitable for treating diseases for which cell-based therapies are a viable option, such as stroke, Huntington’s disease, heart diseases and diabetes.”

The funding, announced by Victoria’s Minister for Economic Growth and Jobs, Danny Pearson MP, enables Dr Abdel Belaidi and Dr Rebecca Nisbet to take advantage of rapid development of mRNA research to pursue their projects.

Dr Belaidi’s work builds on the discovery that some people, despite having gene variants that cause an inherited form of Alzheimer’s disease, are protected from developing dementia.

Dr Belaidi said it would be the first use of mRNA to penetrate the brain and is a technique that could be used to treat other neurological conditions.

“This project not only has the potential to change the treatment landscape for Alzheimer’s disease but also positions Victoria as a leader in the development of mRNAbased therapies, enhancing the State’s reputation as a hub for innovative biomedical research,” Dr Belaidi said.

Dr Nisbet aims to develop a vaccine for Alzheimer’s disease that can stimulate the immune system to produce protective antibodies that function by clearing amyloidbeta from the body and preventing its accumulation in the brain.

“If successful, an mRNA vaccine targeting amyloidbeta will be cost-effective and may enable long-term pre-symptomatic treatment, with the potential to prevent Alzheimer’s disease from developing in later life.

She said the project lays the foundation of establishing a platform for developing mRNA vaccines for neurodegenerative diseases, with the potential to expand Victoria’s mRNA clinical pipeline.

“This is an opportunity for Victoria to develop and grow an mRNA pipeline for vaccines targeting neurological diseases, bringing Victoria to the forefront of innovation for neurological treatments,” she said.

Professor Clare Parish and Dr Chiara Pavan

Some of these cognitive symptoms include changes to thinking, information processing and memory.

Her hope for the future of Parkinson’s disease treatment is to develop a one-off treatment that targets both motor and non-motor symptoms, which would then give Parkinson’s disease patients a more comprehensive recovery from their symptoms.

Cloaked human neural grafts evade immune detection

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The Florey Society Most of us know someone living with a brain-related condition.

Dementia, stroke, Parkinson’s disease, depression and schizophrenia are among the many conditions researched at The Florey.

The Florey Society at the latest boardroom briefing

The Florey Society’s bequest supporters met for the second time this year in June for a research talk by Associate Professor Jess Nithianantharajah, Head of Mental Health Research at The Florey.

Associate Professor Nithianantharajah spoke about the critical importance of discovery to translational research for transforming mental health treatment and care.

A key point of her talk was sharing advancements in behavioural and imaging technologies that are revolutionising how we accelerate the translation of discovery research.

By letting us know you have included The Florey in your Will, you can be involved with Florey Society events recognising your future gift in Will contribution.

Discovery science is key to unlocking the mysteries of the brain and mind. Leave a gift in your Will to help find answers to diseases that affect one in five Australians.

To request our Gifts in Wills guide or to speak to us about your wishes, please contact Nola Wilmot, Bequests Manager on 03 9035 9710 or email nola.wilmot@florey.edu.au

Public lecture for World Brain Day Don’t miss out on our next event Subscribe to The Florey’s mailing list and stay in the loop on the latest breakthroughs, news, events and more.

We were thrilled to host our second public lecture in honour of World Brain Day – an inspiring evening featuring updates on research into multiple sclerosis, motor neurone disease and Parkinson’s disease.

These advances could shape the future of treatments and offer hope to those living with brain conditions.

A thank you to our expert speakers, Dr Arthur Thevathasan, Professor Clare Parish, Dr Shwathy Ramesan, and Dr Thanuja Dharmadasa, and to our incredible lived experience speakers, Les and Linda Clark, who shared how research has already made a tangible difference in their lives.

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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Brain Matters Spring 2025