Congratulations Professor Laura Bennet, Associate Professor Justin Dean, Professor Paul Donaldson, Dr Nicole Moreland, Professor Julian Paton, Dr Raewyn Poulsen, Dr Frederik Pruijn and Dr Rohit Ramchandra
Professor Paul Donaldson
Regulation of lens water transport: A strategy to treat presbyopia and cataract
$4,936,997.70
Globally, 2.1 billion people are presbyopic, and 35 million are visually impaired due to cataract. With a rapidly aging, and increasingly diabetic population, the extent of this burden will rise and increase the cost to the health system. Professor Donaldson’s group has confirmed the existence of a lens microcirculation system. By studying how water transport is regulated in the lens, the researchers will develop novel anti-oxidant based approaches to maintain the optical properties and transparency of the lens, and prevent the onset of presbyopia and cataract.
Professor Laura Bennet
Circadian patterns of fetal heart rate predict impaired fetal oxygenation
$1,199,998.30
Poor growth before birth is associated with a high risk of death and of brain injury. Professor Bennet’s team’s studies suggest that abnormal circadian patterns in the fetal heart rate recordings are associated with poor growth. The project will run clinical and pre-clinical studies to examine fetal circadian patterns in normal and growth restricted pregnancies to determine how and when circadian patterns are related to poor placental oxygen levels. These studies will test for the first time how circadian rhythms can be used to identify high-risk babies with very low oxygen levels before birth.
Associate Professor Justin Dean
Treatment of GABAergic interneuron dysfunction in pre-term brain injury,
$1,186,646.95
Exposure to reduced oxygen and blood flow (hypoxia-ischemia) to the brain in early life is a known trigger for a range of neurodevelopmental disorders, which show common impairments in growth and connectivity of neurons in the brain. We have discovered a new role for the proteins and sugars that surround neurons (the extracellular matrix) in controlling normal brain development.
This study will examine, for the first time, whether abnormal breakdown of a key extracellular matrix sugar, hyaluronan, causes impaired neuron development following early-life hypoxia-ischemia, and whether pharmacological blockade of this abnormal hyaluronan breakdown can promote normal brain development.
Dr Nicole Moreland
Understanding the role of IgG3 in acute Rheumatic Fever
$1,187,148.95
Rheumatic fever (RF) is one of New Zealand’s starkest examples of health inequity, with Māori and Pacific children 20-40 times more likely than all other NZ children to develop the disease. RF is triggered by Streptococcus A (StrepA) infections and can develop into chronic rheumatic heart disease (RHD). There is currently a complete lack of treatment options available to RF patients to halt cardiac damage and progression to RHD.
Improved understanding of RF disease mechanisms is urgently needed to determine pathways that could be targeted by existing drugs to reduce progression. We observed a marked elevation of a particular antibody type (subclass IgG3) in RF patients and will use advanced laboratory methods to map the immune mechanisms associated with this increase. This will identify intervention pathways that maybe interrupted by immune modulating drugs already in clinical use for other diseases with the potential to stop RF patients developing chronic RHD.
Professor Julian Paton
Novel potential anti-arrhythmic target
$1,171,620.25
Heartbeat irregularities are often lethal and can be caused by a group of overactive nerve cells (called stellate) located inside the chest. Removal of stellate cells in humans has been shown to stop life-threatening irregular heartbeats but this involves complex surgery, which is potentially life threatening itself.
In both humans with heart disease and rats with susceptibility to heartbeat irregularity, we discovered a novel drug target or ‘receptor’ on these stellate cells which when blocked stops irregular heart beating.
We propose to identify the precise makeup of this receptor (to refine drug targeting) and the type of stellate cell it resides on. Importantly, we will assess how this receptor makes the stellate cells overactive. In rats we will use a novel drug to block this receptor to see if this safeguards against irregular heart beating. These studies could be translated to humans as a novel treatment for heartbeat irregularities.
Dr Raewyn Poulsen
Turning off the cellular energy supply to treat osteoarthritis
$1,180,501.60
Osteoarthritis is a painful, debilitating disease affecting over 320,000 New Zealanders. It is the most common cause of disability in adults worldwide yet there are currently no drug treatments to cure osteoarthritis or slow its progression. Osteoarthritis is characterised by loss of the cartilage cushion within joints. The cells which normally maintain cartilage become hyperactive in osteoarthritis, aggressively degrading cartilage tissue. This hyperactivity comes with a cost. Osteoarthritic cells must generate more energy than healthy cells.
We propose that limiting the fuel supply to osteoarthritic cells may be a means of limiting their activity and therefore treating disease. Interestingly high blood sugar is a risk factor for osteoarthritis. This may be through increasing the fuel supply to osteoarthritic cells. We will determine how osteoarthritic cells generate energy, whether high glucose aids this process and whether drugs used to treat metabolic diseases e.g. diabetes may be effective for treating osteoarthritis.
Dr Frederik Pruijn
Enabling clinical development of a novel hypoxia-targeted anti-cancer agent
$1,199,945.55
The presence of low-oxygen zones (hypoxia) is a hallmark of many tumours, which confers negative prognosis and poor treatment outcomes after surgery, chemotherapy, and radiotherapy. One way to overcome this therapeutic challenge is via hypoxia-activated prodrugs (HAPs).
We have developed a novel clinical candidate HAP called S-benomycin, which is highly active in many preclinical models of cancer, including of head and neck squamous cell carcinoma (HNSCC). To prepare S-benomycin for clinical trials we will achieve three aims: an inter-species comparison of drug metabolism to inform future drug safety studies; a survey of anti-tumour efficacy across a broad panel of HNSCC models; and development of a new imaging modality, oxygen-enhanced magnetic resonance imaging (OE-MRI), as a companion diagnostic.
We aim to use these data to take S-benomycin into clinical trials in New Zealand in order to improve treatment outcomes in HNSCC patients.
Dr Rohit Ramchandra
Respiratory modulated pacing to improve outcomes in heart failure
$1,191,072.60
A third of people diagnosed with heart failure die within the first year. The survivors have severely impaired quality of life because even day-to-day menial activities leave them breathless and incapacitated. Current treatment options include cardiac pacemakers which help to improve the pumping capacity of the heart. However, these pacemakers lead to fixed changes in heart rate, whereas in reality heart rate is rarely static.
We have utilised a novel cardiac pace-making approach to re-introduce breathing induced heart rate variability and shown improvements in cardiac output. We will now test whether this approach improves respiratory imbalance and exercise tolerance in an ovine model of depressed heart function. This clinically-relevant research will represent a significant step in the development of novel cardiac pacing strategies.