Protecting children receiving chemotherapy from hearing loss

Researchers at Ear Science Institute Australia have developed a novel nano-gel therapy to protect children receiving chemotherapy from hearing loss – a common side effect of the cancer treatment.

The project which involves testing the nano-gel in a new study is led out of Ear Science Institute Australia and supported by funding from the Channel 7 Telethon Trust.

A much-needed preventative approach

Lead researcher, Associate Professor Hani Al-Salami, said about half of children who go through chemotherapy will have some degree of permanent hearing loss due to toxicity of the drugs.

“There is currently no proven prevention or cure for this hearing loss, so this new research will test the effectiveness of a nano-gel that is injected into the ear before chemotherapy to prevent the possible side effect of cancer treatment among children,” Associate Professor Al-Salami explained.

“The nano-gel has been developed in partnership with Curtin University by a group of clinicians, pharmaceutical scientists, ENT (ear, nose and throat) surgeons, cochlea physiologists and synthetic chemists using cutting-edge technologies.

“Human bile extract is put through specialised systems to produce a gel, which is capable of being injected into the human ear. It can potentially protect children from the side effects of chemotherapy, which targets and destroys cancer tissues and can also kill other healthy tissues resulting in problems including hearing loss.”

Associate Professor Hani Al-Salami in the lab
Associate Professor Hani Al-Salami in the lab

Looking forward

Ear Science Institute Australia CEO, Sandra Bellekom, said it was a very exciting time for ear and hearing medical research in Western Australia.

“The Telethon grant will allow Ear Science to further develop an established and proven nano-gel, improving efficacy and making it safer for use in our children,” Ms Bellekom said.

The Channel 7 Telethon Trust’s support of Ear Science Institute Australia also includes funding for the procurement of a newly developed scanning electron microscope for use in the research, which is capable of micro and nano scale visualisation of critical features of the nano-gel.

Blood test measures healthy aging in humans

SAHMRI researchers are the first in the world to develop a ground-breaking new blood test to measure autophagy, the body’s process of recycling unwanted or damaged cells to stay healthy.

The research study, which sheds light on autophagy in humans like never before, has been published in the journal Autophagy.

A peek into biological aging

Dr Tim Sargeant, Neurobiologist at the South Australian Health and Medical Research Institute (SAHMRI), said the effectiveness of autophagy in an individual is the strongest indicator of how well they will age.

“Previous studies have shown that the better autophagy is, the less prone the individual will be to cancer and chronic disease.”

“We think the higher you score on this blood test, the longer you’re likely to live and live well.”

Dr Sargeant

Researchers are confident autophagy holds the key to improving outcomes for those with incurable neurological diseases like dementia by signalling risk factors for the condition earlier.

“If we can learn more about what causes the process of autophagy to stop and start, we can work towards creating life-changing interventions.”

Findings significant in other health fields

Dr Tim Sargeant
Dr Tim Sargeant

The research development is also greatly significant to the future of nutrition and dieting.

It’s widely held that factors such as food and fasting influence autophagy in the body, but science hasn’t been able to prove it in humans, until now. 

“This will lead to us being able to point definitively to what kind of fasting is most effective for people and exactly how much exercise they need to do to increase their autophagy,” explained Dr Sargeant.

“In our view, this is the new frontier of health research and our blood test is really the first step that opens the door to a new world.” 

How the test works

The test involves taking a person’s blood and splitting it into two tubes.

The chemical chloroquine is then added to one of the tubes to stop the autophagy process and by comparing this to the other sample, it’s possible to gage how efficiently autophagy is working.

The test is currently in the early stages of development and requires further investigation into its viability for use with patients.

Researchers are optimistic that autophagy measurement will eventually be included in the standard health check-up, like blood pressure and cholesterol tests.

“Our aim is for the blood test to provide clinicians with a baseline from which to experiment with preventative strategies to increase autophagy in their patients; including everything from lifestyle adjustments to drugs.”

The research was carried out in partnership with collaborators at SAHMRI and the University of Adelaide.

The team are currently undertaking investigations that focus on using the test to measure autophagy in those living with a wide range of diseases, with the aim of understanding how this impacts the disease process.

Predicting relapse in children with cancer

Research at Children’s Cancer Institute has already led to a highly accurate test to predict relapse in children with leukaemia. Now, an equivalent test for children with solid tumours is on the horizon.

Testing for ‘minimal residual disease’

When an Australian child is diagnosed with the blood cancer, acute lymphoblastic leukaemia (ALL), their doctor is almost certain to make use of a DNA-based technique called minimal residual disease (MRD) testing. The test works by detecting and measuring the level of leukaemia cells that remain in the child’s body after treatment begins, and is a powerful predictor of relapse. But for children diagnosed with solid tumours, no such test is available − yet.

‘The key to identifying children at high risk of relapse is to be able to detect even the tiniest quantities of minimal residual disease, as early on in their treatment as possible,’ explained Professor Murray Norris AM, who led the team that developed molecular technology so sensitive it is capable of detecting one leukaemic cell in a million normal cells.

‘This gives the child’s doctor an opportunity to alter treatment well before relapse occurs.’

Professor Norris

When tested in clinical trials, the Institute’s MRD technology led to an effective doubling in survival rates in children with high-risk ALL, and it now underpins tailored treatment strategies for children diagnosed with ALL throughout Australia.

Developing an MRD test for solid tumours

Recent research, published in the British Journal of Cancer, suggests we are getting close to having the equivalent of an MRD test available for children with solid tumours.

Led by Dr Toby Trahair, Clinical Research Fellow at Children’s Cancer Institute and paediatric oncologist at the Kids Cancer Centre, Sydney Children’s Hospital, the research shows that whole genome sequencing (WGS) technology can be used to identify tumour-specific markers, which can be used to detect cancer cells that have survived treatment and will lead to relapse if allowed to do so.

‘To find out if we could use WGS technology as the basis of MRD testing for solid tumours, we looked at data from the Zero Childhood Cancer Program (ZERO), Australia’s first personalised medicine program for children with cancer,’ explained Dr Trahair.

‘ZERO involves extensive molecular analysis of children’s tumours, including WGS, and has given us access to the kind of data we’ve never had before.’

Dr Trahair

‘Our results strongly suggest that using WGS to identify tumour-specific gene sequences is going to lead to a very accurate and reliable way of detecting and measuring MRD in children with solid cancers. And while our research focused on high-risk neuroblastoma and Ewing sarcoma, we believe the findings are likely to be applicable to multiple types of cancer.’

Chance meeting leads to research breakthrough

When WEHI clinician-researcher Dr Charlotte Slade met Cynthia Agius, neither knew it would lead to a research breakthrough and a lasting friendship.

Charlotte

I met Cynthia 10 years ago when I was an immunology and allergy registrar at the Royal Melbourne Hospital. I was struck by what an upbeat person she was, despite having to come into hospital regularly. She was always friendly and grateful to the hospital staff for the care she received. Throughout everything, she has remained positive.

Cynthia has CVID or common variable immune deficiency. It is a condition that impairs the immune system. People with CVID are more susceptible to infection and can develop autoimmune and inflammatory diseases. Meeting Cynthia, and others like her, made me want to learn more about what caused the disorder.

I recruited Cynthia to our research study at WEHI in 2014. I was curious to find out why some patients with CVID developed more severe disease, while others did not. I had a strong suspicion Cynthia’s condition was genetic. Her mother also had CVID and we found that many of her mother’s relatives also had the condition.

“Through our research at WEHI, we discovered that Cynthia’s condition was caused by a mutation in a gene called NFKB1. Pinpointing the exact cause of her condition and being able to explain that to her family was rewarding.”

Charlotte Slade

We screened her children to see if they had inherited the mutated gene and learned that one of her children, a daughter, had inherited the gene, as well as her five-year-old granddaughter.

L to R: Photo of Dr Charlotte Slade (Postgraduate Student; Immunogenetics Research Team; Immunology Division) and patient Cynthia Agius.

Working with Cynthia and her family has taught me a lot about the types of conditions gene mutations can cause. The information about the mutated NFKB1 gene and the ability to screen for it will help people to make better informed choices about their life.

Having a relationship with Cynthia has spurred me on to find answers that might be beneficial for her treatment, or for her children and grandchildren. When you have a personal relationship with your patients, you can’t help going that extra mile for them.

Cynthia

I was diagnosed with CVID 23 years ago. Not long after, my mother was also diagnosed. We didn’t realise it at the time, but many of her 18 brothers and sisters in the Netherlands, and some of their children, also had the condition.

I’d had a lot of infections, but they were always put down to other things. I was getting sinus and chest infections and was in hospital three times a year with pneumonia. Nobody was able to pinpoint the cause. It was not until they realised my immunoglobulin (Ig) levels had dropped to zero that I was sent to see an immunologist and put on monthly infusions of antibody treatments.

Charlotte was one of the registrars at the immunology clinic and we bonded instantly. A few years later, Charlotte asked me to be part of some research she was doing at WEHI. I was honoured to be involved.

Finding out that my CVID was caused by a genetic mutation was a relief in some ways. I am glad that my children were able to be screened. My daughter was diagnosed at a younger age than me, so hopefully she will be better able to better manage her condition.

“It was a breakthrough that Charlotte discovered the mutant gene in our family. Having this information can help patients and doctors make better informed decisions about treatments.”

Cynthia Agius

I have gone through a lot with this condition, but I hope this makes things easier for other families like mine.

Charlotte is a beautiful, caring person. She is more than just a doctor; she has become a friend. We have a special bond that I think will last for many years to come.

Pioneering endocrine hypertension research to be fast-tracked into hospitals

After identifying Primary Aldosteronism (PA) as a significant cause of high blood pressure in Australia, Dr Jun Yang is now leading a multi-state program to equip hospitals to treat this form of endocrine hypertension, which until recently has had a low rate of diagnosis.

As Head of the Endocrine Hypertension Group at Hudson Institute of Medical Research and a Consultant Endocrinologist, Dr Yang heads a project designed to work collaboratively with major hospitals for an expected influx of patients with PA.

The project entitled EQUIPPA aims to equip tertiary care for the optimal diagnosis of PA, and thanks to funding from the Medical Research Future Fund in the recent Federal budget, it’s about to be rolled out in four states over the next three years.

The project was awarded $2,993,294 to be distributed through centres in Victoria, New South Wales, Queensland and Western Australia.

It is also a tribute to Professor Michael Stowasser from the University of Queensland, whose research over the past three decades highlighted primary aldosteronism as an important secondary cause of high blood pressure in Australia.

Prevalence of endocrine hypertension

It comes on the back of the recent study, led by PhD student Dr Renata Libianto, in which GPs tested patients newly diagnosed with hypertension for PA and found that its prevalence was much higher than previously thought.

Dr Yang says it is important to ensure the health system is set up to manage these cases appropriately.

“Before our study, Australian GPs reported less than one in every thousand of their patients had PA, but once they started testing for it, the figure jumped to an astounding one in seven or 14 per cent.”

Dr Yang
Dr Jun Yang

More cases of PA

“If we’re identifying more patients with PA, we need our hospitals and pathology labs equipped to properly diagnose it in a timely, efficient and cost-effective way.”

“We want to prevent the health system from being unable to cope with newly-identified demands,” she said.

This multi-state project is made possible by the work of NSW Health Pathology, Metro South Hospital and Health Service, Qld, PathWest, WA and South East Sydney Local Health District, NSW.

PA patient David Wyatt (whose condition was cured thanks to Dr Yang)

The team encompasses endocrinologists, hypertension specialists, nephrologists, chemical pathologists, radiologists, health economist and Implementation scientists.

As well as the institutions listed above, the EQUIPPA project relies on the work of Hudson Institute of Medical Research, Monash Health, Monash University, University of NSW, University of Qld and University of WA.

Facts

  • In PA the adrenal glands produce too much aldosterone, a salt retaining hormone.
  • As well as high blood pressure, PA increases the risk of stroke, heart attack and kidney disease, despite being rarely diagnosed.
  • PA is frequently undiagnosed and a simple blood test could save more than half a million Australians from unnecessary illness, medication and expense.
  • An Australian-first study led by Hudson Institute of Medical Research, published in the Medical Journal of Australia, found that of the one-in-three Australian adults with high blood pressure (hypertension), at least ten percent have PA.
  • This equates to approximately 600,000 people in Australia.
  • This month is May Measurement Month, drawing attention to high blood pressure, which is the number one cause of preventable death worldwide.

Fathers’ food choices during pregnancy influence future health of babies

What fathers eat during their partner’s pregnancy has a lasting effect on the future health of their unborn children, new research has revealed.

The Queensland Family Cohort (QFC) study, led by Mater Research and The University of Queensland, has shown an urgent need for targeted public health messaging to improve the diets of soon-to-be mothers and fathers.

The researchers examined dietary data from almost 200 couples who were receiving antenatal care at Australia’s largest maternity hospital, the Mater Mothers’ Hospital in Brisbane between 2018 and 2021.

Mother’s diet strongly influenced by Father

QFC Principal Investigator, Professor Vicki Clifton said the study found pregnant women’s dietary intake was strongly influenced by their partner, particularly in the consumption of fruit, vegetables and meat or meat alternatives.

“We know behaviours during the first 1,000 days of life, starting from conception, influence developmental trajectories of adult chronic diseases.”

Professor Clifton

“Healthy eating during pregnancy provides the unborn child with an important foundation for future good health, but many pregnant women aren’t meeting the recommended Australian Dietary Guidelines.

Previously very little research in Father’s diet

“The research suggests better education and support for partners could help improve the eating habits of expectant mums, which in turn will make the foetus healthier and lower their future risk of disease.”

Lead author on the study, Associate Professor Shelley Wilkinson from The University of Queensland School of Human Movement and Nutrition Sciences, said there had been very little research in the past on the role fathers played in a woman’s nutritional journey during pregnancy.

“While it’s known that education, income, and Body Mass Index influence how women eat in pregnancy, this study addresses the gap in knowledge in how a partner’s eating habits influence mums-to-be,” said Dr Wilkinson who was previously the senior maternity research dietitian at Mother Mothers’ Hospital and a recipient of the Mater Research Strategic Grant for Outstanding Women.

“The study also showed women with a higher pre-pregnancy Body Mass Index were far more likely to gain above recommended weight gain ranges, suggesting the urgent need for evidence-informed public health policy and programs to improve diet quality during pregnancy and help prevent intergenerational effects.”

The QFC study findings have been published in the peer-reviewed journal Nutrition & Dietetics.

A very low proportion of participants met the five, core food group intake recommendations.

Only 41.4 per cent of women met daily fruit and 28.4 per cent vegetable intake recommendations, while around 31 per cent and 15 per cent of their partners met these, respectively.

Fewer than one per cent of women and 20 per cent of partners met the recommended intake of serves for breads, cereals and grains and extremely low numbers met pregnancy nutrient reference values (NRVs) for folate, iodine, calcium, zinc, and fibre from food alone.

Brisbane mother of four, Vicki Holohan said her husband Thomas Holohan did influence what she ate during her pregnancy.

“Thomas usually enjoys cooking and often does make a family meal but whilst I was pregnant, I was feeling extra tired and so during that period he was making most of our family’s meal choices,” she said.

“I was always trying to be careful about what I ate, but I definitely relied on Thomas to drive our meal choices during my pregnancy.”

Father’s role starts early

Thomas Holohan said he may have done things a little different if he had known his food choices would flow through to their babies.

Thoman Holohan and his daughter.

“As Dads we get used to thinking our work will begin when the baby is born, but this study shows a father’s role starts much earlier!” Mr Holohan said.

“If I’d known about the influence I would have, I probably would have taken a lot more care with my diet choices – maybe cooking more at home and eating less takeout.”

Data was collected at 22, 24, 28 and 36-weeks’ gestation, and six weeks after the birth of the child.

The collaborative study also involved several researchers from other Australian and overseas-based universities including the University of Newcastle, University of Wollongong, and University of Southampton, United Kingdom.

The Queensland Family Cohort study is the newest birth research cohort in the state in the last 40 years that aims to follow 10,000 Queensland families over three decades to understand the influences on health.

The researchers hope the study will lead to the discovery of biomarkers and interventions that can improve the future health of Queenslanders.

Pregnant women and families interested in joining the Queensland Family Cohort Study can find out more information or join here: www.qldfamilycohort.org

A Hudson Institute researcher has identified problems and potential solutions with new gene targeting medicines that could change the way these are made to help patients.

Headshot of Associate Professor Michael Gantier
Associate Professor Michael Gantier

Gene targeting medicines—nucleic acid therapeutics—are an emerging category of medicine with huge potential to improve the lives of patients. Based on synthetic nucleic acids (DNA and RNA), nucleic acid therapeutics target diseases at the genetic level, by preventing the expression of disease-causing proteins. This new category of medicines could benefit patients by replacing daily medication with injections administered only several times a year.

A study led by Hudson Institute researcher A/Prof Michael Gantier published in Nucleic Acids Research has established that common modifications used to stabilise these nucleic acid treatments are immunosuppressive, meaning that these treatments could selectively block some key sensors of our immune system which normally alert us to infections.

Led by A/Prof Gantier and including PhD student Arwaf Alharbi and Masters student Aurelie Garcin, the study investigated how synthetic nucleic acid molecules interact with the body’s immune system.

“The immune-stimulatory effect of some nucleic acid therapeutics has been known for more than 15 years. However, how these molecules can block the immune response has been understudied,” said A/Prof Gantier.

“We discovered that one class of nucleic acids-based therapeutics was prone to unintended immune suppression, specifically, inhibiting a sensor called Toll like receptor 7 (TLR7),” Dr Gantier said.

“While these molecules are used to target a specific disease, they can also shut down some of the key sensors in the body’s immune response. This could cause strong side effects in patients infected by pathogens after injection with these molecules.”

“If a patient gets the flu or a bacterial infection a few days after getting an injection with nucleic acid therapeutics, this may put them at increased risk of infection. It will only be a problem when a patient gets an infection, so this is a new issue that has not been on researchers’ radar. However, as these technologies become more broadly used, there is an increased potential for patient complications,” A/Prof Gantier said.

Solutions identified

In addition to identifying the problem, the study has also found molecular designs that could be used to avoid these immunosuppressive effects, keeping the immune response in check to defend against infection.

“While we discovered a frequent problem with these molecules we have also provided molecular designs to solve it. This could change the way this new class of therapeutics is made, and help many patients.”

“Many new drugs currently in development based on nucleic acids could be affected,” he said.


More information

What are nucleic acids?
DNA and RNA are a category of molecules known as nucleic acids, which contain and access the genetic information controlling which cells do what in our bodies. Nucleic acids are present in every life form, including bacteria and viruses, and are essential for our immune system to detect infections.

How are these medicines being used?
Several nucleic acid medicines have recently been approved for use in humans, for instance treating some cases of muscular dystrophies. Others are in clinical trials targeting a range of conditions including neurological diseases, cancer, and hypercholesterolemia – which affects about one in 200 people. The therapeutics are also being used to develop anti-viral drugs.

Snoring treatment is found to sharpen memory and focus

Treating the common snoring condition obstructive sleep apnea (OSA) can improve memory, focus and thinking skills. A study by the Woolcock Institute of Medical Research found that patients treated with the ‘gold standard’ OSA therapy can improve not just their sleep, but also their brain function.

The study by the Woolcock Institute of Medical Research in Sydney people found OSA patients who are treated with the gold standard therapy, CPAP, improve not just their sleep but their brain function when awake.

Largest study of its kind

The research, published in the prestigious international journal, Sleep, is the largest of its kind to confirm the brain benefits of the treatment.

“We were able to show improvements to multiple aspects of cognitive function, including working memory, sustained attention and executive function, not to mention improved sleep, mood and quality of life.”

Dr Angela D’Rozario, Lead researcher

More than 775,000 Australians have OSA, a breathing disorder in which the airway repeatedly closes during sleep. Many sufferers wake dozens of times each night as their breathing gets very shallow or even stops. During the day they’re left feeling sleepy and unable to concentrate, and have a higher risk of depression, cardiovascular problems and vehicle accidents.

Symptoms can be reduced with CPAP, or continuous positive airways pressure, which works by holding the airways open while patients’ sleep. However, patients can be reluctant to use CPAP nightly, or stick with the treatment long term.

The Woolcock team enlisted 167 people with OSA to test the impact of CPAP on brain functioning.

“We know that the repeated pauses in breathing that occur during the night in OSA can disrupt sleep patterns and specifically alter different types of brain wave activity that are important for optimal cognitive functions,” Dr D’Rozario explains. “So we thought we’d see whether the main treatment available can reverse this problem.”

Tracking treatment

Volunteers underwent a series of neurocognitive tests at the start and end of the six-month trial, and sleep patterns and brain wave activity were also tracked in two overnight lab stays.

“Excitingly, we found that brain wave patterns during sleep were boosted and performance improved in all areas of cognitive function we tested,” the sleep neurophysiologist says.

“On top of that, self-reported mood, daytime sleepiness, and quality of life relating to sleep also improved after six months of CPAP.”

A driving test simulation

By the end of the trial, patients were getting more deep slow wave sleep and REM sleep, which are important for learning and memory, and more of their in-bed time was spent sleeping. There were also fewer breathing pauses and wake-ups in the night, Dr D’Rozario says.

Impacting brain health

“This shows CPAP can reverse brain wave activity abnormalities during sleep and restore healthy sleep patterns,” she says. “We’re thrilled to see CPAP clearly has a positive impact on brain health. Hopefully this encourages more Australians to use it.”

The team plan to test whether these short term benefits translate to a lower risk of mild cognitive impairment and dementia in the longer term.

The study also involved researchers from Adelaide Institute for Sleep Health at Flinders University and Brain and Mind Centre at the University of Sydney.

Read the paper: Improvements in Cognitive Function and Quantitative Sleep EEG in OSA after Six Months of CPAP Treatment.

Australian first gene therapy for childhood blindness

Two Sydney siblings have become the first patients in the country to receive a novel gene therapy that has rescued their vision and holds hope for preventing them from going blind.

The ocular gene therapy, LUXTURNA, is the world’s first approved gene replacement therapy for an inherited blinding eye condition and one of the first gene replacements for any human disease. Approved by the Therapeutic Goods Administration, LUXTURNA is used to treat children and adults with biallelic pathological mutations in RPE65, a rare mutation that leads to vision loss and blindness. It is being distributed in Australia by Novartis.

Therapy has stopped progressive vision loss

Seventeen-year-old Rylee and 15-year-old Saman were both diagnosed with Leber congenital amaurosis, a severe form of retinal dystrophy, in their first year of life. They received the life-changing therapy at The Children’s Hospital at Westmead in late 2020 and early 2021. The therapy has stopped their progressive vision loss and led to some improvements in their vision.

The therapy was delivered as part of Ocular Gene and Cell Therapies Australia (OGCTA), a new collaboration involving the Genetic Eye Clinic at Sydney Children’s Hospitals Network (SCHN), the Eye Genetics Research Unit and Stem Cell Medicine Group at the Children’s Medical Research Institute (CMRI), and the Save Sight Institute at Sydney Eye Hospital and University of Sydney.

CMRI’s Gene Therapy Research Unit

Revolutionary therapy

CMRI was represented on this project by Professor Frank Martin who is CMRI’s Board President, Professor Robyn Jamieson, Head of the Eye Genetics Research Unit at CMRI and SCHN and Dr Anai Gonzalez Cordero, Head of the Stem Cell Medicine Group and Professor Ian Alexander, Head of the Gene Therapy Research Unit and their teams.

Professor Jamieson is also lead of OGCTA and Head, Specialty of Genomic Medicine, University of Sydney. She said the therapy was revolutionary and would lead to transformation of care for patients with blinding eye diseases.

Professor Robyn Jamieson

“Inherited retinal disease is a devastating diagnosis. Up until now, these patients suffered progressive vision loss that led to blindness and there was no therapy for them at all.”

Professor Jamieson

“But through new genomic diagnostics and the use of ocular gene therapy, we are finding that we have the ability to not only stop this ongoing progression but also help to improve vision for people who have RPE65-related retinal vision loss.”

Children and adults born with a mutation in both copies of the RPE65 gene can suffer from a range of symptoms, including night blindness (nyctalopia), loss of light sensitivity, loss of peripheral vision, loss of sharpness or clarity of vision and potentially total blindness.

Replacing faulty genes

Ocular gene therapy works by injecting LUXTURNA under the retina and carrying a functioning RPE65 gene to replace the faulty one, thereby preventing some of these devastating symptoms.

luxturna Team – the team who delivered Australia’s first gene therapy for a blinding eye condition

“The real-world improvements in visual function has been quite remarkable bringing to life the rather dry clinical trials outcome measures,” said Professor John Grigg, Head of Specialty of Ophthalmology, Save Sight Institute, University of Sydney and lead inherited retinal disease specialist in OGTCA said.

“It is tremendously heartening to see the changes in vision capabilities for these first patients treated with LUXTURNA.”

Professor Grigg

“As an ophthalmologist who has been caring for patients with Leber’s amaurosis for many years and unable to offer any treatment, it is incredibly rewarding to now have the opportunity to not only give families hope but also be involved in improving their child’s vision,” said Frank Martin, Clinical Professor in the Specialties of Paediatrics and Child Health and Ophthalmology at the University of Sydney said.

Associate Professor Matthew Simunovic, Vitreoretinal Surgeon, Sydney Eye Hospital and SCHN and Associate Professor at the Save Sight Institute, University of Sydney performed the first surgery and said the benefits of treatment should extend well into the future.

“This is incredibly delicate surgery in which LUXTURNA is injected under the retina, which in some patients can be as thin as a sheet of copy paper. Riley and Saman have had profound improvements in their vision, which mirror the results seen in the pivotal clinical trials.”

“Importantly, such benefits appear to be sustained for many years – in fact, for as long as patients have been followed up. Successfully delivering the first approved gene therapy has been a fantastic team effort, and it underscores Australia’s capability in this field.”

A/Prof. Simunovic

To date, this treatment has been used to treat four patients and while it can only be used to treat this specific form of retinal disease, it does provide significant hope that similar treatments will be able to be applied to other retinal disease genes in the future.

“This heralds a new era in transforming the lives of these people who otherwise have a life of blindness ahead of them and provides hope for more than 15,000 other affected Australians who live with some form of inherited retinal disease,” Professor Grigg said.

Read more about this story on ABC News.

Melbourne invention brings new hope for rheumatoid arthritis

A new nerve treatment invented by Melbourne researchers at the Bionics Institute is bringing hope to people with rheumatoid arthritis.

The tiny piece of ground-breaking technology – the size of a thumbnail – could replace drug treatment for thousands of people suffering from pain and inflammation caused by the disease.

Living with rheumatoid arthritis

Karen Morgan, 57, who has lived with rheumatoid arthritis for over 22 years says she will be first in line to test the device when it goes into clinical trials.

She said: “The medication makes the pain bearable most of the time, but when I have a flare up it’s a struggle to do anything.”

“Some days my joints are burning hot, stiff and swollen. I find it very hard to walk. I can’t put my car key into the ignition.”

Affecting nearly half a million Australians, rheumatoid arthritis is currently treated using a cocktail of drugs with unpleasant side effects that have severely restricted Karen’s life.

 “The medication has pretty much destroyed my immune system. During COVID I’ve had to avoid people most of the time. It’s been awful.”

Dr Sophie Payne and Karen Morgan

New treatment brings new hope

Amazingly, this new treatment is being developed by Karen’s niece, Bionics Institute researcher Dr Sophie Payne and her team.

Dr Payne says the battery powered device stimulates a major nerve, called the vagus nerve, with electricity to reboot the body’s built-in healing system.

She said: “In rheumatoid arthritis, the body attacks its own joints causing inflammation, pain and stiffness.”

“By stimulating the vagus nerve, which controls the body’s anti-inflammatory reflex, we can dampen the inflammation to reduce the pain and stiffness and allow people with rheumatoid arthritis to move freely.”

Dr Payne

“We’re hoping to take it to clinical trials in just two years,” she said.

Find out more in this interview with Virginia Trioli on ABC and this story in the Herald Sun.

The Bionics Institute

Backed by clinical expertise

Dr Evange Romas, head of the rheumatology unit at St Vincent’s Hospital is working closely with the Bionics Institute team to ensure the device is optimised for his patients.

He says that, in addition to coping with damaging side effects, around 40% of patients stop responding to drug therapy and he is looking forward to the day when he can offer the new vagus nerve device treatment as an alternative.

“I have been involved in some great advances in the treatment of rheumatoid arthritis during my career. However, this new treatment is incredibly exciting and I’m doing everything in my power to help the Bionics Institute researchers get it into the clinic for the benefit of my patients as soon as possible.”

A ‘set and forget’ treatment

Bionics Institute CEO, Robert Klupacs says the beauty of the device is that it can be attached to the vagus nerve in the abdomen using keyhole surgery. And the battery, which sits under the skin at hip level, only needs to be changed every ten years.

 “We’re working towards the day when people with rheumatoid arthritis won’t have to remember to take medication every day and won’t have to cope with side effects.”

 “They can ‘set and forget’ about this electrical vagus nerve device, leaving their body to do the work for them,” he said.

Every donation towards this research will help the Bionics Institute take the vagus nerve device to clinical trials much more quickly and transform the lives of people like Karen.

Find out more

This exciting new nerve treatment was the focus of the Bionics Institute’s recent Rethinking Rheumatoid Arthritis event.

Bionics Institute’s research director Professor James Fallon and lead arthritis researcher Dr Sophie Payne were joined by Dr Evange Romas and specialist in hand therapy Nick Antoniou. To provide their expert insights into the disease and how the ground-breaking new device new device could transform the lives of people living with rheumatoid arthritis. 

Resources

Access the full event recording or view their individual presentations below:

Stem cell-derived organs help better understand and treat disease

MCRI researchers are using cutting-edge stem cell techniques to help treat young patients with kidney disease, and offering hope that one day stem cell-derived kidneys could be used as transplants.

Looking for better options for young patients

Not that many years ago, Charlotte Matthews would have died soon after she was born. Charlotte has congenital nephrotic syndrome, a condition which caused her kidneys to leak a vital protein, making them ineffective

Drugs and surgery kept her alive while she waited for a transplant, but these treatments come with devastating side effects. It’s a painful life for children like Charlotte until they receive life-saving transplants, but it is the best available.

Murdoch Children’s Research Institute’s (MCRI) stem cell medicine and kidney researchers are looking for a better way.

Charlotte’s syndrome was caused by a specific genetic mutation, so MCRI Stem Cell researchers have modelled her disorder in the lab and looked for ways to grow the specific part of the kidney her own body was unable to, called the glomerulus, the kidney’s waste filtering unit.

By studying children like Charlotte, MCRI can develop drugs that will transform the lives of other children like her – and the millions of adults who have less severe disease worldwide.

MCRI researchers want to move kidney disease management towards personalised, stem cell-driven medicine for people across the globe. And they’re inching closer toward that goal each day. 

Charlotte Matthews, 4, is having dialysis to treat her kidney disease. She had one kidney removed when she was a baby and now relies on dialysis to survive, as she waits for a transplant, but is doing great. MCRI researchers have taken cells from her to create a 3D model of the disease to test new treatments. Charlotte Matthews with mother Jessica Taylor. Picture: Jason Edwards

Patient specific mini kidneys

MCRI’s stem cell experts broke new ground in 2018, spearheading research in which stem cells derived from a young patient were grown into two sets of living mini kidneys; one with her kidney disease and another which corrected the gene mutation.

Alex suffers from Mainzer-Saldino Syndrome, a rare genetic condition causing vision loss and kidney failure. Following her diagnosis, MCRI researchers took a skin biopsy from Alex to create stem cells and turn them into kidney tissue. The findings proved the lab-grown tissue can be used to study inherited kidney disease.

The idea is that, one day, the gene corrected kidney-tissue could be transplanted back into the patient from whom it was derived.

The discovery showed the unparalleled value of modelling a patient’s own tissue from stem cells, compared against traditional mouse models of disease.

Using gene editing to correct mutations

Led by MCRI Cell Biology Theme Director, Professor Melissa Little, the group demonstrated that gene editing could correct the mutation and stop the disease developing in the mini kidney.

“Following this result, we wanted to understand how we can use models made from a patient’s stem cells to better understand their disease and find the most appropriate drugs for treatment.”

Professor Little

Disease models created from a patient’s own cells are already helping researchers better understand conditions and develop more precise treatments. But creating enough identical organ models to meet the needs of research teams is a slow and laborious task.

Getting the results faster with the Disease Modelling and Drug Discovery Facility

The MCRI Disease Modelling and Drug Discovery Facility, led by Dr Alejandro Hidalgo, aims to speed up the production line, allowing for increased scale and precision to test new medications and deliver tailor-made treatments.

The Hon Greg Hunt MP visits MCRI to tour the Stem Cell Based Disease Modelling Facility

“With researcher clinicians working across MCRI and The Royal Children’s Hospital we have the invaluable opportunity to work with patients in the clinic and then apply that real world learning within our stem cell labs.”

Dr Hidalgo

Due to funding support received from the Stafford Fox Medical Research Foundation the team have built and equipped those facilities to an industry-leading world standard.

The facility has centralised and enhanced MCRI’s ability to use stem cells models across the eight focus disease areas of kidney, heart, blood, immune system, brain, muscle, reproductive development, and bone and cartilage disorders.

“We have experts working across many of the body’s organs and tissues, making us the largest group of researchers in Australia generating stem cells from a patient’s blood or skin cells.”

Professor Little

3D bioprinting tiny kidneys

In 2020, MCRI researchers reached another milestone when they used a 3D bioprinter to create hundreds of identical tiny human kidneys in the laboratory. This cutting-edge research raised hopes that human tissue printing will one day allow those with end-stage kidney failure to receive a bioprinted kidney instead of waiting for a donor kidney transplant.

MCRI Stem Cell researchers printed the kidneys using a stem cell paste that is fed into a 3D printer. The paste is like a “bioink” to create artificial living tissue in a dish. The mini-kidneys range from as small as a grain of rice to the size of a fingernail, and fully resemble a regular-sized kidney, with hundreds of tiny tubes and blood vessels that form the organ’s filtering structures called nephrons.

The findings of the research were published in Nature Materials. A key part of the study was to test the cells’ response to aminoglycosides, a class of antibiotics that commonly damage the kidneys, as a proof of concept for testing drug toxicities in these assays.

Professor Little said, “Generating stem cells from a patient with a genetic kidney disease, and then growing mini kidneys from them, paves the way for tailoring treatment plans specific to each patient, which could be extended to a range of kidney diseases.”

There is a massive increase in the number of people suffering from kidney disease, but only one in four patients will receive a transplant. That means three in four live on dialysis, an extremely difficult way to live.

“The mortality rate is very high and the quality of life is extremely low,” Professor Little said. “Also, dialysis is still risky as it’s effectively giving you only about 10 per cent of normal renal function. Our hope is that we will find something that is substantially better than dialysis and potentially able to be delivered to the three out of four who can’t find a matched transplant.”

How COVID-19 changed the landscape

SARS-CoV-2 brought a new set of challenges in February 2020. With growing evidence that COVID damages organs beyond lungs, MCRI’s stem cell researchers turned their focus to coronavirus.

The MCRI-led study on the effects of COVID on different organs received a Victorian Government funding boost in 2021 to further its research focus to include emerging strains, long-term symptoms and potential links between the virus and unborn children.

The additional research will build on the MCRI-led project that uses human stem cells to better understand the effects of the virus on different organ systems including the lungs, heart, kidneys, brain, immune system and blood vessels, to support the development of targeted treatments.

The scientists from MCRI, The Doherty InstituteWalter and Eliza Hall Institute of Medical Research and Monash University will now include placental tissue to gain greater insight into the effects of coronavirus on the placenta and potential transfer of the virus to the fetus.

The funding will also see the team investigate cellular mechanisms leading to lingering ‘long COVID’ issues such as fatigue and ongoing breathing problems and analyse international variants to understand the impacts of more infectious strains.

An Australian first

This is the first time research of this kind has been done in Australia, with MCRI one of only a few facilities worldwide able to study the effect of the virus on every major human organ.

Using cutting edge stem cell processing equipment, which recreates human tissues infected with COVID-19, the project has already identified issues with the heart muscle as a result of the virus disrupting oxygen supply.

The Stafford Fox Medical Research Foundation Stem Cell Based Disease Modelling Facility at MCRI also provides capacity to perform rapid drug screening to allow rapid evaluation of emerging COVID-19 treatments.

Professor Little said, “this collaborative program will increase our understanding of disease pathology, identify underlying risk factors, change clinical care to protect the patient from severe complications, facilitate the development of targeted treatment options and better prepare us for the next pandemic.”

Vitamin B3’s promise in slowing glaucoma progress

Promising results in CERA’s pioneering study into the role of vitamin B3 in slowing the progress of glaucoma has sparked plans for a large international trial.

The results of a world-first study, led by former CERA Managing Director Professor Jonathan Crowston and Research Fellow Dr Flora Hui, were published in Clinical & Experimental Ophthalmology in July 2020.

They showed improvement in the visual function of glaucoma patients who received a daily high dose of 3 grams of nicotinamide for 12 weeks in addition to their regular treatment to reduce eye pressure.

Following strong interest in the results, Dr Hui was named as the recipient of Glaucoma Australia’s Quinlivan Research Grant.

The $200 000 funding will be instrumental in supporting the next phase of Dr Hui’s research along with CERA Managing Director Professor Keith Martin and international collaborators including Professor Crowston (now at Duke NUS-Medical School Singapore), Professor Robert Casson from the University of Adelaide, Associate Professor Pete Williams from the Karolinska Institutet, Sweden and Associate Professor Gauti Johannesson from the Umeå University, Sweden.

Dr Flora Hui examining a patient. Credit: Anna Carlile

Protecting nerve cells

Glaucoma is the world’s leading cause of irreversible blindness, affecting more than 60 million people worldwide.

The disease, which leads to vision loss when cells in the optic nerve and retina are lost, is usually treated with eye drops or surgery to reduce eye pressure. However, there are currently no treatments to protect cells from further damage or to improve cell function.

“For the first time, we were able to show that daily high doses of vitamin B3 can lead to early improvements in patients who are also receiving traditional treatments to lower eye pressure.”

Dr Hui

“Our follow-up study will help us determine if vitamin B3 should be taken on an ongoing basis by glaucoma patients,” said Dr Hui

Dr Flora Hui is set to conduct further research to determine if vitamin B3 can slow the progression of glaucoma.

About the trial

CERA’s initial trial followed 57 patients, all of whom received both placebo and vitamin B3 over the course of the study.

The visual function of patients was tested using electroretinography, a diagnostic test which measures electrical activity in the cells of the retina, and visual field testing to determine any changes that occurred.

The trial found that in some people, high-dose nicotinamide improved how nerve cells were functioning in the eye. The follow-up trial will assess whether these improvements can help reduce disease progression over a longer period.

Earlier pre-clinical research in the US showed that vitamin B3 could prevent optic nerve degeneration – but this was the first time similar results have been witnessed in a human trial.

Dr Hui says the findings provide hope of a treatment that could protect nerve cells and damaged cells to function better.

“Like adding oil to a car engine to allow it to run smoothly, vitamin B3 could be used to protect cells from damage and help those that have been affected by glaucoma work better.”

Research supporters

Dr Hui and Professor Crowston’s initial research was supported by the Jean Miller Foundation, Connie and Craig Kimberley Foundation, the Ophthalmic Research Institute of Australia, Jack Brockhoff Foundation, Marian and EH Flack Trust, Fund and Board of Research Faculty (Karolinska Institutet).

Dr Hui is grateful to receive Glaucoma Australia’s Quinlivan Research Grant which will help support the next phase of her research.