Special Research Feature
First steps to gene therapy for Meniere’s disease
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Kidney organoid to drive precision medicine
Breakthrough in blood cancer research
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Northern Sydney Local Health District
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MESSAGE FROM THE ACADEMIC DIRECTOR
I am thrilled to share with you the latest Kolling Institute newsletter, bringing together a collection of stories demonstrating the breadth of high-quality research across the institute. These stories highlight the remarkable teams involved and the impact our researchers are having not just locally, but increasingly on a national and international scale. Our scientists, led by a group of indefatigable senior researchers, are influencing the care our community receives and will receive in the years ahead. They’re making tangible progress across a broad range of disciplines and health challenges facing our community. Our research is informing the development of a unique kidney organoid which is expected to lead to personalised medicine for kidney disease. This approach will be similar to the tailored treatments currently offered to cancer patients. Professor Carol Pollock is leading this extraordinary work with her experienced and talented team. Our researchers are at the forefront of Meniere’s disease science, developing the first humanised model of the disease ahead of gene therapy. To cap off a big year, Professor Jose Antonio Lopez- Escamez received the Nylen- Hallpike Medal at an international conference in Sweden. This award is granted to the world’s best vestibular researcher in basic
science over the last two years and cements our position as a world leading institution in vestibular medicine. Our investigators are making encouraging progress with some of the most challenging cancers, including blood and oesophageal cancer. Discover more about their game-changing work as you read through this feature. A significant point of difference for the Kolling Institute is the depth of our research expertise across the research spectrum from our discovery science through to our translational work. This is clearly evident with our extensive laboratory activity through to our models of care and policy improvements. One example of this is a project led by Professor Trudy Rebbeck offering a musculoskeletal care program to rural and remote parts of Australia. Our researchers including Professor David Hunter and Dr Jocelyn Bowden are also involved in an industry partnership to increase crucial awareness around supplements for osteoarthritis, while Professor Bill Walter is building on the evidence around new ceramic hip replacements. Dr Edwin Tan is broadening our understanding of dementia medications with his large-scale data analysis of existing medication trends.
All of this research is taking place as part of our current research strategy (2021-2025) and I’m pleased to share that we recently held the first of three workshops to review and refresh our next five- year strategy. I would like to thank everyone who took part in the initial workshop for your valuable contributions. It was a good opportunity to hear more about the unique and emerging strengths of the institute and the crucial next steps to increase our research activity and impact. I look forward to the next workshops later this month and early next year, before we finalise our blueprint for the next five years.
Professor James Elliott
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Dr Henry Wu
Kidney organoid to shake up care for the disease
Researchers at the Kolling Institute are making encouraging progress towards personalised medicine for kidney disease, an approach which will mark a significant improvement in care. The team from the Renal Research Laboratory, led by eminent clinician researcher Professor Carol Pollock has developed a kidney organoid, which can be grown from a person’s blood cells or urine in just 10 days. The researchers are believed to be the first team to have developed a kidney organoid from urine. Professor Pollock says their ground-breaking approach will lead to tailored treatments similar to the individual cancer care offered to many patients. “These organoids will be used to test personalised therapies for kidney diseases, determining if a particular drug is effective or toxic for an individual,” said Professor Pollock who is a renal medicine specialist at Royal North Shore Hospital and internationally respected academic with the University of Sydney.
“We will be able to test new therapies that come onto the market to assess whether they could reverse the damage in the kidneys or stop the progression of kidney disease. “We also expect to test whether drug combinations might be toxic to the kidney as we know that some drugs can injure the kidney. “In many cases, people with kidney disease take a lot of medications, and if somebody doesn’t respond well, we often leave them on that drug, and add another one. “We have a handful of medications that have been shown in clinical trials to be beneficial, and in some cases people are on most of these drugs. “But with this new ability to test medications, we will be able to see what works and what doesn’t, reducing the trial-and-error approach in kidney disease management, and replacing it with a potentially life-changing personalised treatment.” Professor Pollock said the development of the kidney organoid is well advanced and they are currently refining how
they would manage the testing. She anticipates its wider use is close. She said their work is an important area of research given the increasing prevalence of kidney disease. “More than 11 per cent of Australians have the condition which claims more lives each year than breast and prostate cancer combined. Kidney disease is a progressive disease which eventually leads to kidney failure and death, without dialysis or a kidney transplant,” she said.
Professor Carol Pollock
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Innovation at the Kolling’s core In the heart of the Kolling Institute, a world-renowned research centre, a raft of clinical trials is driving the future of healthcare. “Clinical trials are intrinsic to
impactful clinical trials. Notably, it has been involved in running multiple trials for those with heart and kidney disease, musculoskeletal conditions and chronic pain. Their cancer trials have made significant contributions across various tumour streams, including pancreatic, haematological, breast, and bowel cancers. James emphasises that basic science, discovery and scientific innovation are embedded in the Kolling’s over 100-year history. “Often, it is those innovations from our basic science laboratories that ultimately inform the mechanisms by which trials are developed.” James adds that understanding the ways diseases work allows researchers to target trials more precisely, leading to better patient outcomes. However, the need for trials sometimes outpaces scientific understanding. “We can’t always wait for a full understanding of a disease,” James notes.
“In some cases, we must move forward with trials to push the needle on patient care, even as we continue to explore the underlying mechanisms.” A key advantage for the institute is its proximity to one of Australia’s largest tertiary hospitals, Royal North Shore Hospital. This connection provides access to a vast patient population, which is crucial for conducting large-scale clinical trials. “We serve over a million patients,” “We want patients to expect that they may be invited to participate in a clinical trial or research study as part of their care.” The Kolling Institute is a world leader in researching osteoarthritis, musculoskeletal conditions, cancer, neuroscience and pain, and cardiac, cardiovascular and renal disorders. says James, stressing the importance of their “trial as therapy” culture.
research,” says Professor James Elliott, Academic Director of the institute. “They help us test something so that we can better inform care for patients with various conditions who come to our hospitals for treatment.” The Kolling Institute has a strong track record in conducting
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Professor Jose Antonio Lopez-Escamez and his research team
Crucial steps towards gene therapy for debilitating Meniere’s disease
Our researchers at the Kolling Institute are at the forefront of Meniere’s disease science developing the first humanised model of the disease ahead of gene therapy. The specialised team is led by world-leading Meniere’s disease researcher and neuroscientist Professor Jose Antonio Lopez- Escamez who relocated from Spain to the institute to pursue his ground-breaking work. His talented team of seven is set to grow to a dozen by 2025. Professor Lopez-Escamez said it was an exciting time for research in this area as we move into precision medicine with specific drugs, and develop gene therapy for the next generation of patients with the disease which causes vertigo and hearing loss. “We are making encouraging progress as we investigate the genetic basis of the disease, finding that many patients have a recessive inheritance where both parents are carriers of the disease but don’t have any symptoms,” he said.
“When I was working as an ENT surgeon in Spain more than 10 years ago, the condition was largely neglected and not well understood, and many patients were not doing well. “Today, we are learning more about the disease and the broad range of influences, including immune-response inflammation, allergy and migraine.” “We are now investigating the genetic mutations involved in the disease in preclinical models in a crucial step towards the development of gene therapy. We believe this game-changing approach will be available within the next 10 years. “Importantly, we must consider that people will have different genetic and immune backgrounds, and different associated conditions, like migraine. “It is not the same disease for all individuals and will present differently.
“We don’t have a magic pill that is going to work for everybody with Meniere’s. For some patients some medication will work, one drug will be better, but for others there will be another way. “That’s why it’s important we know which subgroup of Meniere’s a patient has.” Prestigious International Award Professor Jose Antonio Lopez Escamez received the Nylen-Hallpike Medal at the Barany Society Conference in Sweden. The award is granted to the world’s best vestibular researcher in basic science over the last two years. It recognises the significance of the research underway at the Kolling and the University of Sydney’s position as a world leading institution in vestibular medicine.
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Innovative musculoskeletal program heads to the bush In a sign of the strength of the Kolling Institute’s research and clinical capabilities, Professor Trudy Rebbeck has been awarded a $2.5 million grant to offer a musculoskeletal care program in rural and remote parts of Australia. As a Professor of Allied Health and a physiotherapist, Trudy will lead the collaborative project involving University of Sydney, NSLHD and Kolling Institute researchers Michael Nicholas, Ian Cameron, Annette Kifley and Claire Ashton-James. She is excited to launch the initiative which has been funded as part of a $20 million boost for improved primary care and chronic pain treatment. Trudy said an increasing number of people are experiencing chronic musculoskeletal conditions like back, neck pain and arthritis, but few people in rural and regional areas are being offered evidence- informed care involving good advice and an exercise plan. “We know that people in these communities have poorer access to appropriate care and ultimately poorer musculoskeletal health,” she said. “Our large-scale program, named PACE RURAL, will be offered across the country for the first time, providing a high quality and yet low-cost solution.” It will involve a simple online tool at the point of care to identify people who may recover well and those who may not. Those who are likely to recover well can be
guided by the online resource (Mypainhub.com) which provides accurate advice and exercises to aid recovery. People needing extra care will receive early virtual access to an expert allied health clinician. The allied-health specialist will work with the local GP through an advanced assessment of risk factors and develop an individualised treatment plan. “For many people living in rural and remote parts of Australia, one of the biggest challenges is access to specialised healthcare, so we hope that through this program, we will broaden access to evidenced-based, effective care and importantly, improve long- term musculoskeletal health,” she said.
“We know from our work in metropolitan regions that increasing support from allied- health clinicians delivers better health outcomes for higher risk individuals, so we expect this project will now provide a cost- effective solution in rural and remote Australia too.”
Professor Trudy Rebbeck
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Associate Professor Jenny Wang and her team from the Cancer and Stem Cell Laboratory
Kolling researchers make promising breakthrough with leukaemia study
While there has been a great deal of encouraging progress with many cancer treatments over the last decade, the prognosis for people with acute myeloid leukaemia remains dismal, with only 27 per cent of patients surviving more than five years after treatment. Lead researcher Associate Professor Jenny Wang said we have seen a sharp rise in the number of people with the deadly form of blood cancer in recent years. There are now more than 135,000 people in Australia living with blood cancers, with 16 people losing their life to this disease every day. A/Professor Wang said blood cancers are particularly aggressive forms of cancer and very challenging to treat. “The majority of them are resistant to current chemotherapy treatments which means many people experience a relapse of their blood cancer. If even one cancer stem cell survives after
treatment, the cancer can regenerate and come back,” she said. “Sadly, over 80 per cent of people will experience a relapse with their blood cancer.” The future for blood cancer treatment is expected to be stem cell-based treatment and A/ Professor Wang’s team has made significant progress over the last 10 years broadening our understanding of the biology of the stem cells driving blood cancers. Her Cancer and Stem Cell Laboratory team is using that knowledge to progress the development of an effective, stem cell-targeted cancer treatment. Leukemia stem cells have their own protective mechanisms that make them resistant to anticancer drugs. “Our new treatment approach however, works by disrupting the ability of the leukemia stem cells to self-renew. Specifically, it
destroys the unique protective antioxidant mechanism of malignant stem cells” said A/Professor Wang. “Antioxidants have long been considered a type of healthy compound, due to their many benefits such as anti-aging and anti-inflammatory. However, we found that the antioxidant in cancer protects malignant stem cells against cancer therapy, leading to drug resistance and disease relapse. “Reducing the antioxidant level makes malignant stem cells sensitive to standard chemotherapy and effectively kills these cells. “Encouragingly, it’s anticipated this treatment approach could be applied to other cancers as well, improving outcomes for a much larger range of cancers.”
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New collaboration to drive world leading research into osteoarthritis treatment
An innovative partnership with industry will see our researchers at the Kolling Institute develop evidence-based strategies to improve osteoarthritis management in Australia and globally. Consumer healthcare company Haleon is sponsoring a five-year fellowship to investigate the role of supplements in managing osteoarthritis and digital health technologies to improve mobility. Osteoarthritis is a leading cause of disability, impacting more than two million Australians and 595 million people globally. It represents a significant public health burden particularly among older populations.
The fellowship will fund a postdoctoral researcher to work under the guidance of world leading osteoarthritis expert, rheumatologist and researcher Professor David Hunter. Dr Jocelyn Bowden has been awarded the fellowship and is looking forward to broadening our understanding of the use of supplements and innovative digital technologies. Professor Hunter said the research collaboration represents a shared focus and investment in improving osteoarthritis management. “This is a painful and disabling disease that has a huge impact on the people affected,” he said.
“A collaborative effort between researchers and manufacturers will drive innovation and hopefully improve the lives of those affected by this disease. “Use of supplements and natural ingredients in managing osteoarthritis is an exciting area with a lot of potential. I’m not aware of any other long-term project like this focusing on osteoarthritis.” Dr Bincy Thampi, Medical and Scientific Affairs Lead at Haleon ANZ said they were excited to work with researchers to deliver better management strategies for the disabling disease.
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Practical tool to offer better informed care for people living with dementia
Our researchers at the Kolling Institute are working to improve the use of medications for dementia with a comprehensive analysis highlighting several concerning trends. The latest data indicates more than 420,000 people are living with dementia in Australia, including more women than men. The condition is the second leading cause of death in Australia. Leading researcher and member of the Kolling’s Neuroscience and Pain Priority Research Area Dr Edwin Tan said people with dementia are high users of medications due to the challenging symptoms of the condition and the combination of other chronic conditions. “We found there was often limited evidence for prescribing medications for people with dementia, and clinicians were left to weigh up the risks and benefits of these medications,” he said. “Our analysis of nationwide data found 60 per cent of people with dementia are taking a psychotropic medication like an anti-depressant, antipsychotic or opioid, and 26 per cent are taking an anti-dementia medication like Aricept, Exelon or Reminyl.
“We were interested to find that when we looked at people’s backgrounds, those from a higher socio-economic group were more likely to take an anti-dementia medication, compared with people from a rural or regional area, or those with limited access to healthcare, who were more likely to take a psychotropic drug, like an antipsychotic. “Concerningly, two thirds of people with dementia are taking at least five medications and 23 per cent are taking more than ten medications.” Researchers were also concerned to see the number of high-risk combinations of drugs, with 14 per cent of people with dementia taking all four high-risk medication groups, including sedatives. The data pointed to an increased risk of medication poisoning, with one in five people experiencing an adverse drug event. Researchers identified 15 per cent of people with dementia experienced drug poisoning, compared with just two per cent of the general older population.
Dementia increased a person’s risk of poisoning by an alarming 77 per cent. Dr Tan is now working to develop a personalised antipsychotic calculator to assist with safer prescribing and shared decision making. “Working with patients, clinicians and carers, I am keen to develop a tool which will weigh the risks and benefits of antipsychotic medications to help ensure patients are prescribed the best medication for their individual needs,” said Dr Tan. “An evidenced-based tool, which would predict the likelihood of treatment response and adverse events, could greatly assist personal treatment plans and improve patient outcomes.”
Photo: Dementia image and photo of
Dr Edwin Tan
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Dr Colby Stevenson
Philanthropic funds launch crucial research into little-known cancer
Generous community support is strengthening our research into oesophageal cancer, lifting hopes of improved treatments for the aggressive and deadly cancer. The Fight for a Cure charity has donated $100,000 towards Dr Colby Stevenson’s research, on top of a $100,000 donation from the Howlett family, in memory of their son Scott who died from the cancer. The Howlett family has welcomed the research saying it will help to raise awareness of this little-known cancer, while improving survival rates through earlier detection and treatment Oesophageal cancer is the 11th most common cause of cancer death in Australia, accounting for over 1400 deaths each year. Sadly, less than 25 per cent of people with this cancer survive more than five years, compared to about 70 per cent for all cancers combined.
Dr Stevenson, a surgeon and researcher, said he is incredibly grateful for the philanthropic support as it will allow him to conduct research which would otherwise be very difficult to get off the ground. “There have been some really significant improvements for some cancers like melanoma and breast cancer in the last 10 years, but concerningly, we have not seen the same kind of improvement in outcomes for those with oesophageal cancer,” he said. “Patients will generally undergo chemotherapy and radiotherapy before surgery, with some people responding much better than others. In some cases, the patients’ disease will worsen while on treatment, and occasionally some will not survive it. “My research will analyse oesophageal tumours to look for genes or proteins that may inform a patient’s individual prognosis and if their tumour will respond to a particular treatment.
“This is an important body of work which could lead to individualised treatment approaches and avoid harmful treatments for patients who are unlikely to benefit from them.” Dr Stevenson said he is grateful for this opportunity and driven to progress this research given the current poor prognosis for people with this deadly form of cancer. “I think this type of research could be the key to substantial improvement as it will allow us to further sub-classify oesophageal cancer so we can then develop the best treatment approach for each person,” said Dr Stevenson. If you wish to support to this cause please contact the NORTH Foundation at info@northfoundation.org.au or call (02) 9436 0162 To learn more about Fight for a Cure visit fightforacure.com.au
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Professor Bill Walter
Research driving the development of new implants and improving outcomes
Our researchers at the Kolling Institute have joined with international collaborators to develop a revolutionary implant for hip replacements. The ceramic implant, designed for hip resurfacing procedures, doesn’t require the long stem used in common hip replacements. This means surgeons are not removing the bone which they would generally remove for a hip replacement. Professor Bill Walter, a leading surgeon and investigator with the Murray Maxwell Biomechanics Lab, said that with this approach, the hip feels more natural and is a bit stronger, particularly for activities such as running and jumping.
“Importantly, feedback from patients has informed the development of the device,” he said. “Patients reported excellent pain and symptom relief, and 45 per cent of patients returned to high-level sports.” Female patients also benefitted from the procedure, marking a significant development for the surgery. “In the past, resurfacing has not worked well in female patients but with the ceramic on ceramic resurfacing, we’re getting very good results.” The ceramic device also alleviates concerns around metal toxicity with the traditional implants.
Currently about 50,000 hip replacements are performed in Australia each year, with resurfacing procedures representing less than one per cent. Professor Walter said that trend is expected to change, with up to 50 per cent of patients potentially
eligible for resurfacing. Full Therapeutic Goods Administration approval is
expected this year, with further studies to examine the long-term results of the ceramic resurfacing implants.
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