Dr Susann Beier, Prof John Ormiston, Prof Alistair Young, A/Prof Mark Webster, A/Prof Brett Cowan
Dept. of Anatomy with Medical Imaging, University of Auckland
Heart disease is the most common cause of death in New Zealand. To date, 169,000 New Zealanders are diagnosed with the disease, and every 90 minutes a person dies of its consequences. This fatal damage to the blood vessels around the heart is caused over time and risk factors include a poor diet, smoking, and a family history of heart disease. Stenting treatment is common, but more than 10,000 patients experience complications and 3,000 die suddenly from stent failure. The reason why treatment fails in some patients is because the current generic method is not suitable for every individual. Differences in shape and flow of the patient’s blood vessel influence the success or failure of the treatment. We want to develop a personalised treatment, where individual differences are accounted for. We can achieve this by analysing the data of more than 600 patients. The individual differences can be explored by using a combination of sophisticated super-computer simulations, 3D-printing and radiographic imaging. This allows the testing of different treatment strategies for individuals in the lab, and can help to prevent complications and sudden death rates.
A/Prof Mhoyra Fraser
Dept. of Physiology, University of Auckland
Many preterm infants develop brain injury around the time of birth, with a high risk of life-long disability. Currently, we have no effective way of preventing disability. Our preliminary findings using a well-established animal model of preterm brain injury suggest for the first time that therapeutic manipulation of a critical endogenous neuroprotective anti-inflammatory mechanism can reduce damage to oligodendrocytes, the myelin-producing cells of the CNS. These findings suggest that it is possible to preserve myelination by supporting natural pathways in the brain. However, it remains to be proved whether this therapy will have a sustainable effect long-term. Thus, to replicate and extend our findings we will robustly test the long-term effects of this therapy and determine whether it improves survival of oligodendrocytes, improve myelination and reduce inflammation.
Dr Katie Groom, Prof Lesley McCowan, Prof Frank Bloomfield, Dr Christopher McKinlay
Dept. of Obstetrics & Gynaecology, University of Auckland
Being born too small poses significant risks of handicap and disease throughout a life time. There are no treatments available to improve growth before birth and so the only option is early delivery which adds further disadvantage to long term health. The drug sildenafil may be the first ever in-utero therapy for fetal growth restriction and it is currently being investigated in the STRIDER NZAus clinical trial led by researchers from the University of Auckland. Sildenafil is being given to mothers with pregnancies affected by severe fetal growth restriction across New Zealand and Australia and compared to a similar group of mothers who receive a placebo tablet. The STRIDER NZAus Childhood Outcome Study will follow the surviving babies born to mothers in this clinical trial and will assess the development of these children at the age of 2-3 years. The study will assess whether the use of sildenafil in pregnancy improves the neurological and emotional-behavioural development of these children as well as effects on their cardio-metabolic, respiratory and general health. This study will provide highly valuable information on benefit (and/or harm) as a consequence of antenatal sildenafil therapy for the treatment of fetal growth restriction.
Co-funded with the Neurological Foundation supported by the estate of Mr Daniel O’Brien.
A/Prof Jian Guan, Prof Tim Anderson, Prof John Dalrymple-Alford, Dr Toni Pitcher
Dept. of Pharmacology & Clinical Pharmacology, University of Auckland
Insulin-like growth factor-1(IGF-1) is a hormone and plays a critical role in cognition. A large proportion of Parkinson disease (PD) patients develop mild cognitive impairment (MCI) in part due to poor IGF-1 function. PD with MCI has a 7-fold increased risk of developing dementia compared to those with normal cognition. Parkinson’s dementia is recognised as a primary problem affecting patient and carer well-being and a serious socio-economic issue worldwide. Earlier detection of MCI is critical for initiating effective interventions to delay the onset and slow-down progress of MCI. However there is no, yet an urgent need for, a biomarker to monitor IGF-1 function in order to identify individuals with high-risk to develop MCI and to track cognitive status. Our pilot trial suggested that the increase of plasma cyclic Glycine-Proline (cGP), a fragment of IGF-1 reflects to cognitive status prior to MCI in old people and the reduction of cGP links to PD patients with MCI. We speculate that the changes of plasma cGP may fulfil the role as the biomarker. We propose to evaluate differences in plasma cGP of PD patients with clinically defined normal cognition, MCI and dementia to assess the potential role of cGP as a marker of cognitive function in PD.
FUNDED BY: Anonymous Donor
Dr Anne Jaquiery, Ms Hui Hui Phua, Ms Emma Buckels, Dr Charlotte Oyston
Liggins Institute, University of Auckland
Growth restricted babies have higher risks of perinatal complications in the short-term, and increased life-time risk of developing metabolic disease, such as type 2 diabetes. Thus, the effect of fetal growth restriction can have life-long implications for an individual beyond fetal and perinatal periods. Poor fetal growth often results from placental insufficiency, with the placenta unable to deliver adequate nutrients for fetal growth. Currently, there are no clinical treatments for pregnancies identified as having fetal growth restriction. One medication which may improve placental blood flow, thereby promoting growth by improving fetal nutrient supply, is sildenafil citrate (Viagra). In parallel with the ongoing STRIDER (NZAus) clinical trial, we have completed an experimental study in sheep using an established model of growth restriction. Sildenafil treatment of a ewe carrying a growth restricted fetal lamb improved fetal and placental growth compared to non-treated control ewes. This study will address whether Sildenafil treatment can reverse the increased risk of metabolic disease after intrauterine growth restriction, by exploring the expression of key markers of glucose metabolism in the fetal pancreas, liver, and muscle. This will add to the growing body of knowledge suggesting Sildenafil treatment could ameliorate both fetal growth restriction and the long-term effects of the in utero environment.
Dr Troy Merry, Prof Peter Shepherd, Dr Rinki Murphy, A/Prof Lindsay Plank
Dept. of Molecular Medicine & Pathology, University of Auckland
Obesity and type 2 diabetes (T2D) are amongst the greatest health problems currently facing New Zealand. These diseases are disproportionately greater in Māori and Pacific people than in Europeans. T2D increases the risk of developing other health conditions, including heart disease and liver diseases, and certain cancers. Obesity is the greatest risk factor for the development of T2D and is partly caused by the environment but genetic factors also play a major role. Recently it has been shown that some Samoans have a small change in their CREBRF gene, and this is associated with an increased body mass index (BMI: surrogate measure for obesity), but protects from the development of T2D. We now know that this change in the CREBRF gene is also present in 30-40% of people of Polynesian descent in New Zealand. This study will investigate why people with this change in the CREBRF gene have increased BMI but a decreased risk of T2D. Understanding how genetic variation, particularly one that is unique to people of Polynesian descent, has the potential to determine what factors contribute to obesity and T2D in our population. Such findings are likely to lead to future novel therapeutic interventions in these specific populations.
Dr Nicole Moreland
Dept. of Molecular Medicine & Pathology, University of Auckland
Rheumatic fever is a serious autoimmune disease that can develop after a Group A Streptococcus (Strep A) infection in some children. The rates of rheumatic fever in Maori and Pacific children in New Zealand are unacceptably high and drivers for disease are still poorly understood. This project will use contemporary laboratory techniques to study antibodies circulating in blood to determine the number of Strep A infections patients with rheumatic fever have experienced, compared with healthy children that live in the same area as the patients. The research will answer a fundamental question with respect to how rheumatic fever develops– do children that develop rheumatic experience more Strep A infections than those that do not? Remarkably, given the significant investment in rheumatic fever primary prevention programmes in New Zealand to treat sore throats, it is not known if the number of Strep A infections a child experiences increases their risk for developing rheumatic fever. Or alternatively, whether it is not the frequency of Strep A exposures, but an underlying susceptibility to autoimmune disease that is the driving force. Answering this critical questions will enable future prevention programs and intervention strategies to be designed and implemented with the best chance of success.
Dr Sumudu Ranasinghe, Dr Rashi Karunasinghe, Dr Justin Dean
Dept. of Physiology, University of Auckland
Seizures are the most common form of neurological emergency in newborn infants. Approximately 60% of these neonatal seizures are caused by hypoxic-ischemic encephalopathy, a lack of oxygen and blood flow to the brain, during birth. In New Zealand, approximately 1.3 in 1000 babies that are born at term experience hypoxic-ischemic encephalopathy. These neonatal seizures can increase the risk of developing further brain injury and causing life-long disabilities, including epilepsy. Although the proper management of neonatal seizures is crucial for improving the developmental outcomes for these children, there is currently no effective treatment for seizure inhibition. Indeed, the biological factors that contribute to seizure activity in neuronal cells following hypoxic-ischemic encephalopathy currently remain unclear. Our laboratory has novel evidence that an extracellular sugar called hyaluronan that surrounds neuronal cells may be important for controlling neuronal activity in the brain. We propose that hypoxia-ischemia reduces the levels of hyaluronan in the brain, and leads to increased seizure-like activity in neuronal cells. We aim to test our hypothesis using in vitro and in vivo experimental models. We will also explore whether a pharmacological inhibition of hyaluronan degradation may serve as a novel therapeutic strategy to minimise seizures after hypoxia-ischemia in the newborn.
Co-funded with the Neurological Foundation
Dr Katharine Wallis, Prof Ngaire Kerse, Dr Linda Bryant, A/Prof C. Raina Elley
Dept. of General Practice & Primary Health Care, University of Auckland
Avoidable adverse drug event hospital admissions, adverse drug events and high-risk prescribing in general practice are common, costly and distressing. High-risk prescribing is prescribing that patients at increased risk of harm. The leading risk factor for high-risk prescribing and adverse drug events is the number of medicines a person is taking. Avoidable adverse drug event admissions are increasing as more people are living longer and taking more medicines for more long-term conditions. The most effective, cost effective, and practical approach to safer prescribing in everyday practice is not yet known. We propose a trial to test the effectiveness of an intervention designed to support safe prescribing decisions in everyday practice. The intervention comprises a practice audit to identify patients with high-risk prescribing, education and patient-specific feedback to doctors, and a practice mail-out to patients identified as having high-risk prescribing encouraging them to discuss their medicines when they next see their doctor. If proven effective, cost-effective, and practical, this simple intervention could be rolled out nationally and used routinely by Primary Health Organisations to improve the safety of prescribing and minimise adverse drug event hospital admissions in older people.