Treatment of Parkinson’s disease by simultaneous blockade of DAT and D2-receptors
Professor Brian Hyland, Physiology, University of Otago
Drugs that block dopamine reuptake into brain cells could help treat Parkinson’s disease. However, to date these have produced only mild benefit and are not in common use. Professor Hyland found that the effectiveness of drugs is dampened by negative feedback, which prevents large enhancement of dopamine, but that this feedback can be prevented using small doses of another drug. Professor Hyland will investigate whether this combined therapy enhances limb movement performance in a model of Parkinson’s disease symptoms. This combination may offer an alternative initial treatment, or be used in combination with existing treatments, to reduce their doses and side effects.
MAnagement of Systolic blood pressure during Thrombectomy by Endovascular Route for acute ischaemic STROKE: the MASTERSTROKE trial
Dr Doug Campbell, Department of Anaesthesia and Perioperative Medicine, Auckland District Health Board
Stroke is the third most common cause of death in New Zealand and is one of the leading causes of long-term disability at all ages. A life-saving clot retrieval procedure can save lives and prevent disability of patients with ischaemic stroke who get to hospital in time. In NZ, 90% of clot retrieval procedures are performed under general anaesthesia. Many anaesthetic drugs can affect blood pressure (BP) and blood flow within the brain. Increasing BP during the procedure could provide additional benefits in this devastating disease. A large trial is needed to investigate BP management during clot retrieval.
Rescue of a spectrum of brain injury & behavioural deficits due to extreme prematurity
Associate Professor Dorothy Oorschot, Department of Anatomy, University of Otago
Associate Professor Oorschot’s research aims to investigate whether specific treatments rescue the brain injury of extreme prematurity. Specifically, she will investigate if these treatments prevent myelin loss and the loss of ADHD- and hearing-related nerve cells in the midbrain. She will also investigate if these treatments prevent memory deficits, hearing deficits, and ADHD-like hyperactivity. Associate Professor Oorschot will use an innovative, clinically relevant model that was developed at the University of Otago and published in the prestigious international journal, the Journal of Neuroscience. A positive outcome would drive clinical trials to develop effective treatment for the brain damage and behavioural deficits of extreme prematurity.
Identification of the range of suppressive checkpoint ligands expressed by Glioblastoma cells that directly control T cell activation
Dr E Scott Graham, Department of Molecular Medicine, University of Auckland
Glioblastoma multiforme is a brain cancer with a median survival of less than 15 months. It effectively evades detection by our immune system and one way it does this is through the expression of suppressive proteins that control T cell responses, which are trying to kill the cancer cells. The goal of Dr Graham’s current work is to analyse a panel of Glioblastoma cultures derived from New Zealand patients who had this devastating brain cancer with the hope to identify the range of suppressive proteins (called checkpoint ligands) that these cells express to control and evade the immune-system.
MRI-enhanced EEG biomarkers of cognitive impairment in Parkinson’s disease
Professor John Dalrymple-Alford, Department of Psychology, University of Canterbury
Parkinson’s disease (PD) is more than a motor disorder. It often impairs thinking and memory (i.e. cognitive ability); this decline can ultimately progress to dementia. Professor Dalrymple-Alford will examine the electrical activity of the brain (“EEG signals”) using electrodes placed on the scalp. This will describe patterns of communication across functional brain networks, aided by structural and functional brain scans to specify their neural sources. Some patterns will represent a bio-signal that identifies patients showing severe cognitive impairment. Such “biomarkers” will enable early assistance and identification of those patients at greatest risk of losing their ability to think clearly.
Small project grants
A pilot study of high resolution nerve ultrasound for ‘in vivo’ diagnosis of genetic and acquired peripheral sensory and motor neuronopathies
Dr Luciana Pelosi, Department of Neurology, Auckland DHB
Sensory-neuronopathy is a disease of the nerve cells of dorsal root ganglia, causing degeneration of nerve fibres in the peripheral nerves and spinal tracts conveying sensory information to the brain. Non-invasive techniques allowing accurate diagnosis of this disease do not exist. Dr Luciana Pelosi has recently found that patients with two inherited types of sensory neuronopathy have characteristically ‘small’ nerves on ultrasound. This is distinct from the ultrasound abnormality reported in all other diseases affecting peripheral nerves. This project investigates if ‘small-nerve’ abnormality is also characteristic of other types of inherited and acquired sensory and inherited motor neuronopathies, providing a scope for a larger-scale project to establish nerve ultrasound as a non-invasive accurate diagnostic tool for these conditions.
Potential use of lithium to treat Huntington’s disease
Professor Bronwen Connor, Pharmacology and Clinical Pharmacology, University of Auckland
Huntington’s disease (HD) is a genetic neurodegenerative disorder that results in the loss of brain cells found in the striatum. Currently there is no treatment to prevent or reduce the progressive cell loss that occurs in HD. One cause of cell death in HD may be a loss of the protective factor BDNF due to the genetic mutation causing HD. Professor Connor’s project will investigate whether lithium can reduce cell death in HD by restoring BDNF levels. This will be investigated using a novel technology that allows us to generate brain cells from the skin tissue of patients with HD.
i-Motifs as transcriptional regulators: Potential transcriptional regulation of the serotonin transporter by a non-canonical DNA structure
Dr Darren Day, School of Biological Sciences, Victoria University of Wellington
Depression and anxiety are a significant social problem that arise from both genetic and environmental influences that alter the way the brain responds to chemicals (neurotransmitters) the body produces. Many medications for treating depression prevent the reuptake of the neurotransmitter serotonin by inhibiting the serotonin transporter, and hence are known as selective serotonin reuptake inhibitors (SSRIs). Dr Day will investigate how differences in the part of our DNA that codes for the serotonin transporter can make us more or less likely to suffer from depression or anxiety.
New avenue for increasing responsiveness to radiotherapy in IDH1 mutant glioma
Dr Dean Singleton, Auckland Cancer Society Research Centre, University of Auckland
Each year primary brain cancer kills 250 New Zealanders. Recent discoveries have shown that over 75% of lower-grade brain cancers are caused by a mutation in a metabolic enzyme, isocitrate dehydrogenase 1 (IDH1). Mutated IDH1 produces a cancer-initiating molecule called 2-hydroxyglutarate (2HG), which interferes with many vital functions in the cell, encouraging the affected brain cells to become cancerous. In this project Dr Singleton will study how IDH1 mutant brain cancer cells respond to radiotherapy and test a new strategy for boosting cell killing by interfering with the processes that repair DNA after it has been damaged by radiotherapy.
Developing human astrocytes to model neurodegenerative diseases
Dr Indranil Basak, Department of Biochemistry, University of Otago
Batten disease, the most common inherited neurodegenerative disease in children, shares symptoms with Alzheimer’s disease, Parkinson’s disease and epilepsy and diagnosis is often difficult. Treatment options are palliative, aimed at protecting the dying neurons. Recent evidences in brain research have shown that supportive cells in the human brain, like astrocytes, are also affected in neurodegenerative diseases. It is unknown if these affected astrocytes cause neuronal death. Dr Basak’s aim is to develop pure human astrocytes in a dish to mimic Batten disease, which will not only reduce animal model dependency, but will also be a valuable tool for other neurodegenerative diseases.
Optimizing Anaesthesia for Clot Retrieval in Ischemic Stroke
Dr Fiona McBryde, Department of Physiology, University of Auckland
New Zealand physicians have been at the forefront of refining and implementing a revolutionary new stroke treatment, which involves physically removing an occluding blood clot from the brain. Recent research has shown that patient recovery is better if this procedure is performed under general anaesthesia, but it remains unknown whether the particular type of anaesthetic may be better for stroke patients. New research by University of Auckland scientists will determine whether the choice of anaesthesia can help protect blood flow to the brain during clot retrieval surgery and ensure the best possible recovery for stroke patients.
Investigating spinal cord stimulation using electroencephalography
Dr Matthew Moore, Department of Anaesthesiology, University of Auckland
Clinicians have used spinal cord stimulation (SCS) for decades to provide relief to patients with intractable chronic pain. SCS is poorly understood, it does not work for everyone, and the complications are too common. Dr Moore plans to investigate the brain’s electrical response to SCS, using electroencephalography (EEG) in participants with SCS. Participants will have their EEG recorded while therapeutic SCS is delivered. A better understanding of brain activity during SCS could lead to improvements in SCS therapy and in the selection of patients likely to benefit from this treatment, plus offer insights into SC physiology, with wide-ranging therapeutic applications.
Tyrosine Kinase Inhibitor Encapsulated Nano‐formulation for the Treatment of Glioblastoma Multiforme
Dr Manisha Sharma, School of Pharmacy, University of Auckland
Glioblastoma multiforme (GBM) is the most common form of brain tumour. With minimal treatment options, mortality rates are high and average prognosis is only 15 months survival after diagnosis. The available front‐line medicines are not effective in patients due to the presence of treatment‐resistant cells. This project aims to develop a novel nano‐carrier formulation loaded with antitumor drug Sunitinib. The developed formulation will be tested on patient‐derived GBM cells for its effectiveness. Dr Sharma envisions that this nano‐formulation will have the ability to enhance the efficacy of the drug and show selective cellular toxicity to the brain tumour cells.
The spatial and temporal heterogeneity of primary central nervous system (CNS) tumours pre and post treatment - a prospective multidisciplinary study
Dr Komal Srinivasa, Consultant Histopathologist, Auckland City Hospital
$81,660 - Dr Srinivasa will be based for one year at the Department of Neuropathology at the Washington University School of Medicine with clinical attachments at Barnes-Jewish Hospital, St Louis, Missouri
Brain tumours pose a serious health burden in New Zealand and affect both adults and children. Treatment is not always possible and remains difficult due in part to our limited understanding of the variety of different types of brain tumours. This multidisciplinary project will study the impact of brain cancer on affected people and combine this information with analysis of their imaging (scans) as well as the microscopic appearance of the brain (histology) and the accompanying genetic changes. It is a long-term project, which hopes to provide novel information to understand and ultimately improve the patient outcomes from these tumours.
Advanced neuropathology training
Dr Alastair Murray, Consultant Anatomical Pathologist and Cytopathologist, Canterbury Health Laboratories
$6,211 - Dr Murray will undertake six weeks of training with Professor Colin Smith, Western General Hospital, Edinburgh
Neuropathology is the detailed examination of brain, spinal cord, peripheral nerve, and muscle tissue to try and establish the nature and prognosis of diseases affecting these organs. Dr Alastair Murray will be receiving advanced training in neuropathology under Professor Colin Smith at a world class centre for neuropathology training and will bring these skills back to the New Zealand public through his work as a consultant pathologist at Canterbury Health Laboratories in Christchurch.