Brain Matters Autumn 2024

Brain Matters

Your source of neuroscience and mental health insights from The Florey

Tribute to a visionary

Harold Mitchell AC 1942-2024

The Florey was saddened by the passing of Harold Mitchell AC at the age of 81 in February.

Harold was The Florey’s valued and deeply committed Board Chair from 2012 to 2020, setting us on a new and exciting path for our brain research with vision and vigour. He served as a Governor since then.

Harold was known across Australia for his immense influence as an advertising and media buying executive; he believed in our mission and the pursuit of discovery and offered wisdom, charm and boundless energy

He was hugely proud of The Florey, and was a very generous philanthropic donor whose substantial donations have supported our scientists to conduct world-leading research. Harold considered researchers to be ‘heroes’, working for the good of human-kind.

It has been an incredible privilege to have had Harold as part of The Florey. In his honour, we continue in the pursuit of knowledge of the brain and scientific excellence that he so passionately championed.

Vale Harold Mitchell AC

A new era for dementia treatment

New amyloid treatments for Alzheimer’s disease will bring immense challenges and exciting opportunities, a gathering of leading figures in dementia has heard in Melbourne.

Researchers, members of the health, aged care and pharmaceutical sectors met recently at The Florey to hear how amyloid therapeutics are likely to change dementia treatment in Australia.

Although the new class of treatment has been proven for the first time to slow down Alzheimer’s disease in clinical trials, some questions remain around its benefits – who will be eligible, side effects, cost, infrastructure requirements, the impact on the health and aged care workforce and other challenges.

One step closer to a blood test for diagnosing Alzheimer’s

A Melbourne study showing the efficacy of a simple blood test to detect the earlier stages of Alzheimer’s has brought us one step closer to a ‘game-changer’ for dementia diagnostics.

Australian Dementia Network (ADNeT) researchers at The Florey with collaborators at Austin Health, University of Melbourne and CSIRO, showed 90% accuracy for the diagnosis of Alzheimer’s through the ‘pTau217’ blood test, which looks for a protein called ‘phosphoTau’ in the blood. This form of tau builds up in the brain as Alzheimer’s develops.

While the tests are not yet commercially available, they are being trialed by ADNeT and Florey researchers with people attending memory specialist clinics in Melbourne, Sydney and Hobart and in selected primary care locations to confirm their value in routine specialist and primary care practice.

This work has led to the installation of the pTau217 test at The Florey, which will be available by April to researchers and for clinical trials around Australia.

In the studies, participants from the Australian Imaging Biomarkers and Lifestyle study of Ageing (AIBL)a research program led by The Florey and ADNeT - were tested, showing that pTau217 can accurately detect Alzheimer’s in the brain even before symptoms develop. It also shows promise for separating people with either intermediate or advanced stage Alzheimer’s from those at a early stage, providing prognostic information and informing better selection for clinical trials and new

Australia’s Minister for Health and Aged Care, the Hon. Mark Butler, spoke of how in the past 20 years, dementia’s prevalence had skyrocketed, transforming it from a fringe issue to the core business of aged care.

He said while lecanemab, the first amyloid therapeutic to be granted US FDA-approval, represented a ‘light at the end of the tunnel’, it was not a cure.

“What we were dreaming of 10 years ago has the potential to become a reality. It’s not a cure, it’s a diseasemodifying therapy,” Minister Butler said.

Florey Director Professor Trevor Kilpatrick said now was a pivotal time for Alzheimer’s disease treatment, which is fragmented across different parts of the health and aged care system.

“This class of therapies will require an enormous shift in healthcare

disease-modifying therapies.

The studies also showed the substantial cost reduction that can be achieved using blood pTau217 compared to PET scans to select participants for clinical trials even before symptoms develop.

Professor Christopher Rowe, lead researcher, said: “These studies show that blood pTau217 immunoassays can be done accurately on widely available equipment. It is likely to be approved by the US Food and Drug Administration this year for clinical use and will be the first blood test fully approved for detection of Alzheimer’s disease. We expect that Australian TGA approval that will enable this test to be used in clinical practice will not be far behind.”

The results align with those from a recent Swedish study by the University of Gothenburg, which showed that a commercially available blood test could detect the presence of tau proteins with an accuracy more than 90%.

The blood test work that The Florey is involved in is funded by the Medical Research Future Fund, NHMRC Centre for Research Excellence and the Commonwealth Department of Health and Aged Care.

delivery for a large patient base. But there are huge opportunities here for both patient welfare and for acceleration of impactful research to develop even better therapies.”

There are an estimated 300,000 people in Australia with Alzheimer’s disease, but lecanemab has only shown benefit in patients in the early stages of the disease.

Professor Kilpatrick said Florey Alzheimer’s expert Professor Colin Masters had played an important role in dementia research, discovering alpha beta amyloid, the peptide that accumulates in the brain and is an essential component of Alzheimer’s disease.

Read more about the event and watch the video by scanning this QR code:

Professor Christopher Rowe

Rare diseases

Rare diseases are life-threatening or chronically debilitating disorders that affect fewer than 1 in 2000 people.

Although the occurrence of each individual condition may be low, more than 2 million Australians are living with a rare disease (Australian Government, Department of Health). These diseases often involve many complex symptoms and require a range of specialised treatments.

Around 80% of rare diseases are genetic in origin and the onset of symptoms can range from early childhood to adulthood. 70% of diseases start in childhood.

The impact of a rare disease on a person’s life and their family can be devastating. Diagnosis can often take time and for many of these diseases there are no effective treatments or cures.

Over 6,000 rare diseases are characterised by a broad diversity of disorders and symptoms that vary not only from disease to disease but also from patient to patient suffering from the same disease. The fact that there are often no existing effective cures adds to the high level of pain and suffering endured by patients and their families.

Which rare diseases are we investigating at The Florey?

Dr Lauren Bleakley

HCN1 gene-related epilepsy

is a rare genetic epilepsy that affects young children including babies who can have up to 20 seizures a day, as well as severe developmental delays.

“I have seen first-hand the hope that our research can provide for patients and their families,” says Dr Lauren Bleakley.

“Gaining a better understanding of how rare genetic mutations disrupt normal brain function can lead to more informed treatment decisions being made for these patients, which can have significant positive impacts on their lives.”

Dr Ya Hui Hung

Niemann-Pick Disease type C (NP-C) is one of over 100 genetic conditions that cause childhood dementia. Due to errors in the affected gene, children born with NP-C will gradually lose their ability to think, move, and speak as they develop devastating early onset dementia.

Currently, NP-C is incurable, and half of these children will not live past their teenage years.

“My team’s research focuses on developing a new mRNA gene therapy to deliver a healthy copy of the gene to the brain, to stop the neurological damage,” says Dr Ya Hui Hung.

“If we can achieve this, it will give children living with NP-C and other genetic conditions causing childhood dementia a hopeful future and allow them to live a fulfilling life.”

Professor Tony Hannan

Huntington’s disease, neurofibromatosis and Prader–Willi syndrome include symptoms affecting brain function, cognition and behaviour and have a huge impact on affected individuals and their families. For these diseases, we have no fully effective disease–modifying therapy or cure.

“As each disease has specific genetic causes, we can model and understand each disease in great detail. It allows us to identify candidates for new therapies that we can test in our validated preclinical models,” says Professor Tony Hannan.

“Our new understanding of these rare diseases will help us understand more common related conditions affecting the brain and mind, including autism, ADHD, schizophrenia, depression, anxiety disorders and dementia.”

Science across the generations

“When I first met Marie I was very much a newbie,” says Florey PhD student Chaseley McKenzie.

“I was in awe of having the privilege to learn from and work with someone who not only is extremely experienced in the field, but whose passion and enthusiasm for science is unwavering.”

Chaseley says that now, after knowing Dr Marie Phillips, 82, for just shy of five years, she is still just as inspired by her as the day she met her.

Dr Marie Phillips just retired as a senior research officer in the Ion Channels and Diseases Group at The Florey.

While many of us decide to hang our lab coats up at 67, Dr Phillips says the beauty of the world kept her going.

“I have always found the world around me wonderful. I have even driven home at rush hour and found myself looking at the buildings, roads, cars and thinking ‘an animal did this.’

“The human brain with its billions

Read more

about the rare diseases we study here:

Professor Steve Collins

Creutzfeldt-Jakob disease (CJD) is a rare human form of one of the transmissible spongiform encephalopathies, also referred to as prion disease. Prion disease can occur as a chance event but can also be found in rare causes attributed to a genetic mutation or be acquired through a transmission event.

Professor Steve Collins says CJD is the most common of human prion diseases.

“Although rare, prion diseases are a frequent differential diagnostic consideration in patients with subacute cognitive decline and their mechanisms of replication and transmissibility are recognised as directly relevant to much more common neurodegenerative disorders such as Alzheimer’s disease.”

Professor David Finkelstein

Multiple system atrophy (MSA) shares many Parkinson’s diseaselike symptoms. It is a rare degenerative disease that affects movement, breathing, blood pressure and other body functions.

Around 3,000 people in Australia live with MSA. Currently there is no cure and there are very limited treatments. The average prognosis after diagnosis is currently less than 10 years.

“People with rare diseases often feel alone”, says Professor David Finkelstein.

“It is important to let people know that scientists around the world are working to improve the lives of people living with MSA.”

“We have been working on a compound for more than 10 years and it is now in clinical trial. It is hoped that the compound is effective in improving the lives of people with MSA. The results of the trial should be released late 2025.”

of connections and the struggle to understand its complexities. We are putting one more small piece of information in the giant puzzle.”

Following time in the UK and Canada, Dr Marie Phillips returned to Australia with a Commonwealth Scholarship to do a PhD.

Forty-three years later Dr Phillips is still involved with and fascinated by neurological diseases involving genetic mutations. In 2008 she joined the Florey at 66 years of age, working with Professors Steven Petrou and Chris Reid.

“This group working on epilepsy had many fascinating ion channels

Dr Sarah Gordon

Named after the Florey researcher Dr Sarah Gordon, and her colleague who first identified this disease, children with BakerGordon syndrome can experience developmental delays, involuntary movement, poor or no speech and behavioural difficulties. This rare neurodevelopment disorder is caused by a mutation to a protein called SYTI leading to slow neural communication.

“It’s been an honour and privilege to work with the families of people with Baker-Gordon Syndrome.”

“There is currently no treatment or cure for this rare neurodevelopmental disorder – most children impacted by this disorder never learn to talk, and many never walk. The goal of my lab is to understand this and other rare disorders, in order to develop treatment strategies.”

Professor Brad Turner

Professor Brad Turner and his team are investigating how nextgeneration DNA designer drugs called antisense oligonucleotides (ASOs) could be used to target and suppress the androgen receptor gene linked to Kennedy’s disease. It is an inherited neuromuscular disorder that causes progressive muscle weakness, wasting and physical disability in men.

“Kennedy’s disease is a low-profile disease with no treatment or cure,” says Professor Turner.

“Our hope is to improve the lives of people and families impacted by Kennedy’s disease.”

“We are privileged to be working closely with the Kennedy’s disease community to develop a precision medicine approach, leveraging our unique patient-derived cell and models established at The Florey.”

to work on, a close association to clinical and pharmaceutical groups, good equipment and a great working environment,” Dr Phillips said.

In the last few years, key members of the team Dr Phillips works in have made important advances in sudden unexpected death in epilepsy (SUDEP). One such advance is the discovery that genetic changes that compromise regular heart rhythm increase the risk of SUDEP.

“The more we know, the more we find is out there waiting to be discovered,” Dr Phillips said.

“However not by me. It is time for me

to leave and find another adventure. Thanks to the Florey and especially Professor Reid for letting me work here for so long.”

PhD student James Petrou, who works closely with Dr Phillips in the lab, says he strongly recommends that younger and older scientists engage with one another.

“Younger scientists engaging with older scientists is beneficial not only on a practical level of getting particular perspectives on your projects and methodology, but also in gaining a greater appreciation for why it is we do what we do.”

Life after stroke

By Professor Julie Bernhardt

Stroke is one of Australia’s leading causes of death and disability. More than 400,000 Australians of all ages are currently living with stroke, and by 2050 that number is projected to rise to 800,00.

People who have survived a stroke may face many challenges sensing, moving, thinking and communicating.

“Most people who have had a stroke will live with some visible or invisible consequences, but research shows that the kind of care they receive can make all the difference.”

Families, communities, support organisations and aged care providers all play an important role in supporting those who’ve experienced a stroke. Recovery can take a long time, and support needs to be ongoing.

At The Florey, we’ve been working to improve outcomes for people with stroke for many decades. Clot busting and clot retrieval treatments for people with acute stroke due to a clot are now ‘usual care’ and have made a huge difference to patient outcomes.

The important message to access these interventions is to get to hospital FAST. This acronym is coined from the symptoms of stroke – drooped face, difficulty raising arms and slurred speech, as well as it being time-critical to get medical attention.

We have also been testing different approaches to improving rehabilitation environments, services and interventions to help improve outcomes for people affected by stroke.

We know that while recovery can continue for months or even years after stroke, there is a period after stroke in which the brain seems to be most receptive to positive change. This appears to be in the first five to six weeks, and lessens over time.

This is not to say that positive changes are not possible later, but it does emphasise that what happens in the first few months after stroke is important.

Below we outline just a few areas of research we’ve been exploring to improve outcomes for people with stroke.

The rehabilitation environment

Stroke rehabilitation environments are critical spaces for recovery but have received little attention.

In fact, rather than encouraging stroke survivors to be active, many facilities inadvertently encourage them to stay in their rooms, often in bed and alone. This isolation can have serious consequences at a time when the goal is to optimise engagement, activity and practice of lost skills to optimise recovery. Instead, hospital environments should provide:

• a positive and stimulating environment

• communal spaces and destinations that encourage people to get up and be active

• access to and a view of the outdoors

• personal control over their environment and activity.

Earlier rehabilitation after stroke

For many years, and still in many countries, the start of rehabilitation is delayed or access to some form of rehabilitation is poor.

We have spearheaded research that aims to find the safest and most effective type and amount of rehabilitation to kickstart recovery of mobility very early after a stroke. Around 80 per cent of people who have a stroke have problems with moving and walking. We are trialing different early mobility training protocols in 42 hospitals in 7 countries.

With more than 530 patients in the study so far, our goal is to roll out the best clinical protocols across the world.

This article was first published in Aged Care Today

Paving the way for MS treatments

Florey researchers Associate Professor Justin Rubio and Dr Sarrabeth Stone have been awarded a combined total of $900,000 to propel research looking into treatments for multiple sclerosis.

Associate Professor Justin Rubio has been awarded $650,000 from MS Australia for research leading to new effective drug targets that aim to slow or prevent progression of the chronic central nervous system disease, multiple sclerosis (MS).

The researchers will identify the genes involved in repairing the damage caused to myelin – a substance that wraps and protects parts of our brain cells – by inflammation that occurs in the brain of people living with MS. These are the genes involved in the progression of MS, the most difficult stage of MS to manage.

Making headlines with a discovery that could help a global drug shortage

Semaglutide is part of the glucagonlike peptide-1 (GLP-1) receptor targeting family of peptide drugs, which are mainly used to treat diabetes but are difficult and expensive to make.

An international team of researchers led by Professor Akhter Hossain at The Florey has developed a new faster and cheaper method to synthesise GLP-1 receptor targeting drugs.

Professor Akhter Hossain, Head of The Florey’s Insulin Peptide Laboratory, said the discovery published as the cover article of the Journal of Medicinal Chemistry could mean cost-effective and high-scale production in the future.

“Semaglutide has proven to be more efficient than other anti-obesity drugs, in terms of weight loss and safety, and this has led to it being in short supply.”

“We set out to develop an improved and cost-efficient synthetic process for making a potential new drug to target the GLP-1 receptor. Semaglutide has a very ‘hydrophobic’ component in its structure, meaning it’s not easily dissolved in water and thus challenging to manufacture.”

The team used a chemical process called ‘glycosylation’, which differs to the ‘lipidation’ process used to make

semaglutide, to make an analogue of GLP-1 that is ‘hydrophilic’ and much more easily dissolved.

“Glycosylation resulted in tenfold higher yields compared with semaglutide,” Professor Hossain said.

Postdoctoral researcher in Professor Hossain’s laboratory, Dr Chaitra Chandrashekar, said it was exciting to be involved in research that could lead to benefit millions of people in the future.

“Our short-term experiments in animal models showed our potential

drug performed as semaglutide would. It significantly lowered blood glucose levels and promoted enhanced glucose disposal,”

Dr Chandrashekar said.

“The method we’ve developed has fewer chemical steps and better yield than the current process for making semaglutide. Although more research is needed, it appears to be a way to rapidly and easily synthesise new drugs like semaglutide, while retaining their major therapeutic benefits for blood glucose control,” she said.

“We are seeking to increase understanding of the biology driving MS progression through gene discovery and translate this into therapeutic targets for medicines that can repair damage caused by inflammation in the brain,” Associate Professor Rubio, Head of the Neurogenetics Group, said

“It is expected that this will build the case for translation into clinical trials where newly developed drugs are tested in people living with progressive MS in the hope of slowing or preventing progression.”

Dr Sarrabeth Stone was awarded $250,000 to investigate how microRNA can be used to direct microglia to efficiently repair myelin.

MicroRNA is a small molecule produced within our cells that controls cell function by regulating gene expression, and is dysregulated in MS.

“This research will open new avenues to novel therapies that promote and repair regeneration in the brain and spinal cord of people with MS,” Dr Sarrabeth Stone said.

Current treatments can reduce symptoms in some types of MS, but they do not prevent long-term damage and do not work in all people with MS, particularly those with progressive forms of MS.

New treatments that protect and repair the brain are desperately needed to prevent the accumulation of disability caused by myelin damage.

Dr Sarrabeth Stone

Professor Justin Rubio

Dr Chaitra Chandrashekar

Donor Mary Semple gets creative for The Florey

In 2017 Florey donor Mary Semple started making calendars from Cherry Tree Grove Retirement village. For the last seven years, she has donated a portion of the earnings to The Florey.

“I have always loved taking photographs and we have a very pretty lake around the village,” Ms Semple said.

“I love the moods of the lake in the various seasons and I said to a couple of people I would love to make a calendar of some kind.”

Ms Semple said she encourages the people in the village to email her a photo they think might be suitable. She keeps them on file and uses ones that are suitable for each month.

“It is a very pretty village so I’ve usually got something nice to put in.”

“I pay for them myself and cross my fingers that I’ll sell them all and I do!”

“I work really hard, I have to put notices in the Cherry Tree Chatter, and I have to remember to get in there by the 15th of the month. I have friends who help produce it as well as my daughter.”

Ms Semple’s husband sadly passed away a few years ago due to a rare form of Parkinson’s disease. She has always supported the work of The Florey, an Institute she says she has always known about.

In her spare time Mary also teaches French, and for years she was an English/French teacher at schools in Melbourne. Merci beaucoup Mary!

Giving to support the future of brain and mind research

One in five Australians are affected by neurological and mental health conditions. For many current medications and treatments do not work Every day, our world class researchers at The Florey are working to find new ways to diagnose, treat and prevent these conditions and help those in need.

Become a Florey supporter

Every donation to The Florey, no matter what the size, helps us develop new treatments, advance our understanding of the brain, improve healthcare and find new ways to assist our communities. You can give to specific areas of research or to a general support fund. Donations can be made via our online giving page or by contacting the Philanthropy Team who can help you decide what you would like to support.

Include a gift in your Will

Including a gift in your Will provides a legacy of hope, ensuring a lasting contribution towards a better future. The decision to leave a bequest is a meaningful way to support medical research, and help improve the quality of life of those who live with brain-related conditions. See our website for details.

Join us for our public lectures

Every year The Florey hosts a free lecture series that is open to the public. You can come and hear from our experts about their latest research. Sign up to our online newsletter on our website to receive an invite when registrations open.

Upcoming events

•New approaches for treating mental health conditions

Tuesday 25 June, 5.30pm Prof Ashley Bush, Prof Anne-Louise Ponsonby A/Prof Jess Nithianantharajah

Thank you to our donors

Without the generous support of our donors, we would not be able to continue our ground-breaking research. Your donation helps our researchers to make a difference every day. We are extremely grateful to all our generous donors. For further information on how you can support us, please contact our team.

Email: philanthropy@florey.edu.au Phone: 1800 063 693

Find out more www.florey.edu.au/support-us

Acknowledgement of Country

Find out more by scanning this QR code:

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.