Auckland Medical Researchers Given $1.24million To Progress Vital Work

Using bacteria to improve cancer treatments, predicting what tumours will recur, the link between anaesthesia and delirium, using an eye test to diagnose ADHD and engineering new antibiotics are among 10 research projects given $1.24 million in funding from Auckland Medical Research Foundation.

The December granting round covers a wide range of health conditions from new-borns to the elderly. The projects are rigorously evaluated by the foundation’s Medical Committee, a panel of independent clinicians and scientists who use an established criteria to rank and decide which research projects should be awarded funding.

It takes the charity’s total investment in medical research in 2022 to $4.13million.

“The calibre of medical research being done in Tāmaki Makaurau is impressive and we are proud to be part of the quest to advance medical treatments and improve the quality of life of thousands of New Zealanders,” Sue Brewster, chief executive of AMRF, says.

“Through the curiosity and tenacity of these researchers, we may find cures, improved treatments, and greater understanding of a wide range of conditions. But this cannot happen without investing in research. This funding gives them assurance they can continue their vital work.”

The projects focus on:

• Investigating whether a simple eye test can diagnose ADHD in children,
• Improving ways of predicting which central nervous system tumours are most likely to recur
• A clinical trial of breathing in pre-schoolers who suffer from wheezing
• Whether engineered bacteria can help fight cancer by enhancing immunotherapy
• Widening a cancer trial of an enzyme that sabotages immuno-therapy treatments
• How gut bacteria affects immune cells in new-borns and allergies and auto immune disorders later in life
• Understanding cochlear damage through 3D imaging to greater understand hearing loss
• Trialling an anti-inflammatory drug on babies with a brain injury as a result of loss of oxygen or blood supply at birth
• If 'light' rather than 'deep' anaesthesia during surgery could reduce rates of postoperative delirium
• Discovering if compounds can be added to existing anti-biotics that have become ineffective, to combat the looming global health crisis

Auckland Medical Research Foundation (AMRF) supports medical researchers and their projects, led out of the greater Auckland region. As well as two annual granting rounds, AMRF also funds travel grants for researchers to attend national and international conferences or laboratories; doctoral scholarships for students embarking on their PhDs; postdoctoral fellowships as the next stage of a research career after PhD completion; repatriation fellowships to mid-career researchers to return to New Zealand, bringing back knowledge and skills, along with other awards that enable researchers to study offshore.

December 2022 granting round projects

Bugs as drugs

Dr Alexandra Mowday, The University of Auckland, Auckland Cancer Society Research Centre

$179,984, 2 years

Immunotherapy is a cancer treatment that helps direct the immune system to fight cancer. However, only a small number of patients benefit from it.

Those that do respond, typically have large numbers of immune cells within their tumour, suggesting if it was possible to recruit additional immune cells to the tumour, it would improve the effectiveness of immunotherapy for more people.

Many immunotherapies have autoimmune-related side effects that can vary in severity.

A bacteria offers a unique solution to improve how the immunotherapy is tolerated and how effective it is.

This research will look at whether the engineered active bacteria can provide specific and continuous delivery of immunotherapy from inside the tumour – minimising the potential side effects, and if it can recruit more immune cells to tumour tissue to make cancer immunotherapy more effective. If successful, this approach could produce meaningful results for a significant number of patients who do not respond to immunotherapy.

Dopamine deficit and vision testing

A/Prof Monica Acosta, The University of Auckland, Optometry and Vision Science

$179,977, 2 years

Could a simple eye test help diagnose attention deficit hyperactivity disorder (ADHD) a condition that affects an estimated one in 20 New Zealanders or 280,000 people including 2-5% of children?

ADHD starts in childhood but untreated, can extend to adulthood with increased risk of anxiety, depression, substance abuse, learning disabilities and sleep problems.

While it is one of the most common disorders affecting children, getting a diagnosis and treatment for ADHD is often described as ‘prolonged and traumatic’.

This research will investigate whether eyes hold biomarkers – biological clues – that could guide a more precise objective diagnosis of ADHD in children.

Dysfunction in dopamine and its pathways play a major role in neurological disorders, including ADHD. It was the most frequent diagnosis assigned to Māori children accessing mental health services in 2009-2011 (Ministry of Heath, 2013).

“Our experimental approach will determine whether examination of the eye and visual function serves as objective biomarkers for ADHD, to facilitate early and targeted treatment in children to greatly improve wellbeing of those affected by ADHD.”

Cochlear vasculature

Dr Haruna Suzuki-Kerr, The University of Auckland, Physiology

$179,250, 2 years

There is no intervention to prevent or delay the onset of hearing loss, a condition that affects more than 800,000 people in New Zealand. Hearing is dependent on the auditory neurons located deep inside the organ of hearing, the cochlea. They are in turn critically dependent on the delivery of nutrients and oxygen by blood vessels.

However, the fine network of small blood vessels supporting these neurons has not been well researched. To fill this gap of knowledge, the collaborative research team will use a novel combination of 3D imaging techniques to investigate deep inside the cochlea. This will research how tiny blood vessels surround auditory neurons and how they develop and change with age, fundamental in understanding how auditory neurons may be affected by changes in blood flow following damage or surgical interventions.

“In the long term, this will help us develop new diagnostics and therapies to optimise the health of neurons in the cochlea, to prevent deterioration of hearing in people starting to experience hearing loss and to preserve nerve function in patients with cochlear implants.”

Prevention of wheeze-associated hospitalisation in preschoolers

Prof Cameron Grant, The University of Auckland, Paediatrics, Child and Youth Health

$177,984, 2 years

Preschool wheeze is a common cause of hospital admission of preschool-aged children worldwide and the most common cause in New Zealand and Australia. Prevention strategies are ineffective and potentially harmful.

An orally medication that stimulates immune responses against viral infections and reduces respiratory inflammation has been proven to reduce infections in children, in placebo-controlled trials, however larger studies are required to evaluate whether it prevents wheeze-related hospitalisations.

More than 2,200 children aged 1-5 with a history of wheeze who are admitted to participating Australasian hospitals (including seven in New Zealand) will take part in another placebo-controlled trial to determine the efficacy for preventing hospitalisations in preschool-aged children.

Tregs and SCFAs

Dr Gergely Toldi, The University of Auckland, Liggins Institute

$174,675, 2 years

Regulatory T cells (Tregs) are immune cells that play a critical role in balancing the immune response. But little is known about how these cells evolve in early life.

Using samples of term and preterm babies, tests will be done to explore how short chain fatty acids (SCFAs) – metabolic products produced by harmless bacteria in the gut – influence the development of regulatory T cells.

The results could help fight immunological complications affecting newborn babies, as well as allergies and autoimmune disorders in later life.

Balanced-2 study

Dr Carolyn Deng, Auckland District Health Board, Anaesthesia

$156,046, 2 years

Delirium is the most common serious postoperative complication, occurring in an estimated one in four older adults undergoing major surgery. Delirium causes significant distress to patients, whānau and hospital staff, and is associated with prolonged hospital stay, physical decline and progression to dementia-like illnesses.

A population-based study in New Zealand shows that Māori patients are more likely to experience delirium at a much younger age after surgery. The conditional funding for this 2023 study comparing 'light' to 'deep' anaesthesia during surgery, to see if 'light' general anaesthesia could reduce rates of postoperative delirium. Previous literature suggests that targeting 'light' anaesthesia may reduce delirium rates by up to 25%. Over 10% of adults aged 70 years and over undergo surgery each year and this simple, cheap, and readily-available treatment could reduce disability, preserve brain health and well-being of many older adults in New Zealand and worldwide as well as save millions of healthcare dollars.

Optimising meningioma prognostication

Dr Clinton Turner, Auckland District Health Board, Anatomical Pathology

$80,707, 2 years

This project hopes to identify improved ways of predicting which central nervous system tumours are most likely to recur, which may improve outcome through closer follow-up and/or early additional therapy.

A meningioma is a primary central nervous system tumour that begins in the brain or spinal cord. While regarded as “benign”, it may have devastating consequences such as blindness, permanent weakness and even death. A major issue with meningioma management is the difficulty in predicting which tumours may recur.

This research will assess various testing methods, including a free, newly-developed “Auckland meningioma score” to assign recurrence risk with the objective of identifying the best use of healthcare resources, and improve the quality of care following meningioma surgery.

Arylformamidase in cancer

Dr Petr Tomek, The University of Auckland, Auckland Cancer Society Research Centre

$60,000, 2 years

Immunotherapy is the future of cancer care. By stimulating the patient’s immune cells to fight cancer cells, immunotherapy can cure cancer. Yet this does not happen in most patients because the cancer sabotages their immunity.

Two key saboteurs are enzymes IDO1 and TDO. They produce the chemical kynurenine that paralyses cancer-killing immune cells. To sensitise patients to curative immunotherapies, kynurenine needs to be stopped however that is proving harder than anticipated.

This research, co-funded by the Health Research Council, sets out to inactivate the enigmatic enzyme arylformamidase required by both IDO1 and TDO to make kynurenine.

It has generated promising results in ovarian cancer cells so this research will test it in a diverse range of cancer cell types.

Exendin-4 after hypothermia

A/Prof Joanne Davidson, The University of Auckland, Physiology

$49,500, 2 years

This research aims to improve health outcomes and the quality of life of our youngest, most vulnerable New Zealanders – babies that have brain injury as the result of the loss of oxygen or blood supply at birth. This can lead to death or life-long disability. The only treatment available for these babies is brain cooling – hyperthermia – but nearly half of those babies will still develop brain injury. Treatments that can be used alongside brain cooling are urgently needed to improve the outcomes.

Previous research has shown that there is unresolved inflammation in the brain, even after treatment with hypothermia. This inflammation likely contributes to brain injury and disability.

This research, co-funded by the NZ Neurological Foundation, aims trial and anti-inflammatory drug Exendin-4 alongside brain cooling. The AMRF funding will go towards fellowship working expenses.

”Ultimately, we hope to reduce the risk of life-long disability and improve the quality of life for these babies and their families, and to reduce the financial burden on the healthcare system.”

Antibiotic hybrids

Prof Brent Copp, The University of Auckland, School of Chemical Sciences

$10,000, 18 months

Antimicrobial resistance (AMR) is a global health threat. Since their introduction in the 1940s, antibiotics have been the cornerstone of modern medicine, saving lives by being able to cure infectious diseases and prevent infections in those that are immune compromised.

There has been an increase in the incidence of antibiotic-resistant bacteria, driven by inappropriate prescribing and the ability of bacteria to adapt to, and overcome, the action of antibiotics.

Rates of some infectious diseases in Māori and Pacific peoples are about twice as high as in those of European descent and other ethnic groups, and rates are significantly higher than average in the youngest and oldest age groups, and in the most socioeconomically disadvantaged New Zealanders.

This project will investigate whether compounds can 'rehabilitate' old antibiotics, restoring their effectiveness to aid in the fight against drug-resistant bacterial infections.

It has the potential to stimulate a genuine advance in global health sciences and medicine.

• AMRF was established in 1955 and has invested more than $90million into a wide range of medical research. With all of the foundation’s administration expenses covered by a generous benefactor, this ensures 100% of all donations goes directly to medical researchers and research projects.

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