Significant University research funded by Health Research Council

The grants announced on 30 June include: 

Professor Alistair Gunn, Faculty of Medical and Health Sciences

Pathogenesis, detection and treatment of perinatal brain injury
60 months $4,999,982.55

Perinatal brain injury is the single greatest cause of disability over the whole of life. The team played a key role in developing brain cooling, now the first established therapy for injury after low oxygen levels at term. However, cooling is effective only in a limited window of time, and is unlikely to be suitable for extremely preterm infants. They have now shown that brain lesions can develop weeks after a period of low oxygen and that the lesions are preceded by local inflammation, raising the tantalising possibility of effective late treatment. Using established fetal sheep models we will evaluate promising anti-inflammatory and trophic interventions to prevent this late brain injury and to improve brain development after early treatments such as cooling. We will test new algorithms to predict the onset of late brain injury, to help clinicians target therapy to babies who may benefit from new treatments.

Professor Stuart Dalziel, Faculty of Medical and Health Sciences
RCT budesonide-formoterol reliever therapy in moderate/severe childhood asthma
36 months, $1,439,964.30

Childhood asthma is a major public health problem in New Zealand. The evidence base for the treatment of childhood asthma is considerably less than for adult asthma. In adults, treatment with a single inhaler that contains both preventer and reliever medications, used as-needed for asthma symptoms, is markedly better at reducing asthma attacks compared to the common approach of taking a reliever-only inhaler as-needed for all asthma severity. This new treatment regimen has not been studied in children with moderate and severe asthma. If comparable efficacy with as-needed preventer+reliever inhaler treatment is shown in childhood as with adult asthma, then implementation of this approach would markedly reduce the burden of asthma in children. In this randomised controlled trial, undertaken in partnership with community general practitioners, the effect of the combined budesonide+formoterol inhaler taken as-needed will be compared with salbutamol as-needed in children aged 4-11 years with moderate and severe asthma.

Dr Joanne Davidson, Faculty of Medical and Health Sciences
Is Exendin-4 neuroprotective after perinatal hypoxia-ischaemia?
36 months,$1,199,443.45

Low oxygen and impaired blood supply to the brain (hypoxia-ischaemia, (HI)) around birth is associated with death, brain damage and disability in about 2/1000 live term births in New Zealand. Brain cooling (therapeutic hypothermia (TH)) is now well established to improve survival without disability but is only partially effective and must be started within six hours of birth. Thus, the challenge is to find treatments to augment hypothermic neuroprotection as well as neuroprotective treatments that have a longer window of opportunity for effective intervention. Recent evidence suggests that the type 2 diabetes mellitus drug, exendin-4, has neuroprotective properties but this has not been demonstrated in large animal translational models. Excitingly, our preliminary data in fetal sheep, suggest that exendin-4 significantly improves the recovery of brain activity after hypoxia ischaemia and critically, augments neuroprotection with therapeutic hypothermia.

Professor John Fraser, Faculty of Medical and Health Sciences
A vaccine for Staphylococcus aureus
36 months, $1,199,789.30

Staphylococcus aureus causes hospital and community acquired disease world-wide and the steady rise of antibiotic resistant strains of S. aureus is of global concern. New Zealand has amongst the highest rates of staphylococcal disease in the developed world and with the ever-increasing failure of antibiotics, other options such as vaccination are vital. It is widely agreed that sterilizing immunity towards S. aureus is not possible, but a prophylactic vaccine to reduce the incidence and severity of infection is possible. We have developed a vaccine that generates blocking antibodies against a set of important virulence factors called the Staphylococcal Superantigen-Like (SSL) exoproteins. We seek to develop this vaccine towards human clinical trials.

Associate Professor Michael Hay, Faculty of Medical and Health Sciences
Hypoxia-selective delivery of DNA-PK inhibitors to tumours
36 months, $1,199,999.65

Radiotherapy, in combination with chemotherapy, is used to treat advanced head and neck squamous cell carcinoma (HNSCC), but tumour control within the radiation field is limited by normal tissue toxicity and tumour hypoxia. We have identified novel DNA-PK inhibitors which sensitise HNSCC cells and tumours to radiation. We will exploit the presence of hypoxic cells in HNSCC tumours using prodrugs to selectively deliver the DNA-PK inhibitor. We will prepare and evaluate a series of prodrugs in HNSCC models to identify a lead prodrug. We will develop models of the behaviour of the prodrug in tumours and predict the best way to administer the prodrug. We will evaluate the prodrug's ability to radiosensitise HNSCC tumour xenografts and determine the advantage the prodrugs provide through sparing normal tissue and selectively killing tumour cells. We will work with Māori groups to identify pathway to equitable clinical application of this novel prodrug.

Dr Hakkan Lai, Faculty of Medical and Health Sciences
Climate change, heat exposure and child health
36 months, $1,199,999.10

Exposure to hot temperatures, even in cooler climates, can lead to significant adverse health outcomes. An estimated 37% of recent heat-related deaths globally have been attributed to human-induced climate change. In New Zealand, the effects of climate change have not been studied in detail. Nevertheless, based on overseas evidence, the burden of heat-related mortality and morbidity in New Zealand children is likely to be substantial and inequitably distributed. We will study the effect of hot weather on child health: birth outcomes (preterm birth, stillbirth), infant mortality, emergency room visits and acute hospital admissions in children aged 0-5 years. We will investigate factors that may increase heat exposure or vulnerability to heat contributing to health inequalities. We will estimate the burden of disease potentially attributable to heat exposure in children in recent and future decades under climate-change temperature-increase scenarios. We will suggest policy measures to reduce impacts on vulnerable sub-populations.

Associate Professor David Newcombe, Faculty of Medical and Health Sciences
The evaluation of treatment outcomes for methamphetamine dependence in Aotearoa
40 months, $1,199,839.40

Methamphetamine (MA) is the second most commonly used illicit drug in Aotearoa New Zealand (NZ). Regular/heavy users are likely to develop a dependence syndrome and experience a range of physical and psychological adverse effects; many will return to using following attempts at abstinence. Given these adverse effects some people who use MA are likely to want or need to access treatment to help them reduce the harms associated with their use, and to ultimately quit. However, the availability of effective treatment options, and the evidence about what works for problematic MA use is limited. The aim of this research is to improve our understanding of what treatment approaches reduce MA use and related physical and psychosocial harms, and to identify the predictors of positive treatment outcomes in NZ.
 

Associate Professor Jacqueline Ramke, Faculty of Medical and Health Sciences
How can we improve eye, hearing and feet-health for kaumātua/older adults?
36 months, $1,200,000.60

Older adults commonly experience sensory impairment due to their eye, hearing or foot health, particularly if they also live with diabetes. Most of this impairment is preventable or treatable, but there are significant inequities in access, management, and health outcomes for Māori and Pacific kaumātua. This project will use a population-based cross[1]sectional survey to measure the magnitude, social distribution and co-occurrence of diabetes, eye, ear and foot problems for adults in Northland, Counties Manukau, Tairāwhiti and Lakes. We will refer people for relevant health care services as required and assess in 6 months whether they were able to access care, key barriers and enablers to engaging with healthcare services and the impact this has on outcomes. The findings will inform the design of whānau-centered, integrated care that reduces the burden on individuals and whānau, improves health outcomes, supports healthy ageing, and prevents inequities.
 

Dr Rachel Webb, Faculty of Medical and Health Sciences
HCQ4ARF: A Randomised Trial of Hydroxychloroquine for Acute Rheumatic Fever
48 months, $1,437,916.85

Acute Rheumatic fever (ARF) is an immune-mediated inflammatory condition triggered by the bacterium group A streptococcus, affecting the joints and heart valves. In approximately 50% of cases ARF leads to permanent heart damage known as rheumatic heart disease (RHD). Approximately 150 Māori and Pacific children suffer from ARF each year in New Zealand. Four-weekly intramuscular penicillin injections prevent relapses, but there is no proven treatment that effectively reduces heart damage. Hydroxychloroquine (HCQ) has been safely used for many decades to treat rheumatological conditions such as systemic lupus erythematosus. Recent studies have shown that HCQ reduces inflammation in the blood of ARF patients. In 2019, two New Zealand patients with severe ARF were treated with HCQ, both with favourable responses. This trial involves randomising approximately 150 New Zealand children with ARF to receive either HCQ or placebo for 6 weeks, to see if this reduces inflammation and early heart damage.

Honorary Associate Professor Elana Curtis, Faculty of Medical and Health Sciences
Mā te mōhio ka mārama (M2M). Impact of Covid-19 on Māori:non-Māori inequities
36 months, $1,197,495.85

This study will document the impact of COVID-19 pandemic management on Māori:non-Māori inequities in health at both a nation-wide and regional level. Health experts are concerned that the health system’s response to the pandemic may have exacerbated existing non-COVID-19 inequities. This relates to disruptions to ‘business as usual’ healthcare, how the healthcare system ‘re-started’ following the first outbreak and community concerns in seeking healthcare. M2M is framed from a Kaupapa Māori positioning and includes a quantitative analysis of national data sets ‘pre’ and ‘through’ COVID-19. M2M will examine categories of access to health care, quality of health care and health outcomes. Findings are expected to inform health policy and practice interventions to support pro-equity and Treaty of Waitangi compliant approaches to future pandemic management within NZ.

Dr Gerhard Sundborn, Faculty of Medical and Health Sciences
Is acute rheumatic fever primarily caused by scabies? A case-control study.
36 months, $1,189,100.15

Increasing evidence suggests that acute rheumatic fever (ARF) is primarily caused by scabies infestation. (Scabies leading to Group A Strep infection in skin leading to ARF) Scabies is an important cause of health inequality in NZ, almost exclusively affecting Pasifika and Māori children. It leads to scarring of heart valves, and often, early death. Rash associated with scabies is confused with skin diseases, such as eczema or insect bites. Building on findings from our 2019 HRC Pacific project study that found scabies infestation common in early child education centres in south Auckland (50-60%) we propose a case-control study which may dramatically change the focus for ARF prevention in NZ, with a focus on scabies. The study will compare evidence for scabies infestation among cases of ARF and their families with population controls. This could prevent over 200 cases of ARF each year and address massive inequities Pasifika and Māori children.