July 2009 Grant Round Recipients

Neurological Foundation Announces July 2009 Grant Round Recipients

The Neurological Foundation of New Zealand awarded more than $800,000 in research grants, travel grants and scholarships for its July 2009 funding round, announced on Friday, July 3. A further $300,000 was awarded under the University of Auckland, Centre for Brain Research Douglas Research Grant. The Foundation also awarded its second Repatriation Fellowship, a scholarship established to encourage young scientists working abroad to return to New Zealand to continue their careers.

“The grants funded reflect the depth of research being undertaken throughout New Zealand,” said Neurological Foundation executive director, Max Ritchie.

“They range from a pilot study into virtual rehabilitation in schools for cerebral palsy, a clinical trial for a brain cancer vaccine, anti-addiction compounds to signaling systems in the brain. It is an impressive body of work and indicates the world-leading expertise of New Zealand’s neuroscientists.”

“The Foundation also wants to acknowledge the generous contribution to neuroscience made by Graham Douglas. His generosity as allowed more projects to be initiated in this round, and he is helping us to give hope to the many people throughout New Zealand who suffer from neurological disorders,” Mr Ritchie said.

Neurological Foundation Repatriation Fellowship

Tuning Cortical Excitability to Promote Neural Repair and Regeneration After Stroke

Dr Andrew Clarkson

Department of Anatomy and Structural Biology

University of Otago

$85,000

Stroke is the leading cause of adult disability. Brain damage caused by a stroke affects related parts of the body, such as speech, vision, and paralysis. However, recent studies show the brain tries to repair itself to a small extent after an injury. It does this partly by remapping brain functions to undamaged parts of the brain, and forming new connections in the brain tissue next to the area damaged by the stroke.

Preliminary studies have led to novel and effective therapies that promote function in partially damaged brain areas after injury. These therapies either reduce the action of an inhibitory neurotransmitter system, the GABA system, or increase the action of an excitatory neurotransmitter system, the AMPA system. This study will further assess these systems in terms of drug delivery and remapping of brain regions for development as a clinical treatment.

The Neurological Foundation of New Zealand Human Brain Bank

Prof Richard Faull Department of Anatomy with Radiology

University of Auckland $86,835 The Neurological Foundation of New Zealand Human Brain Bank was started in 1993 to provide for the collection of human brain tissue to facilitate and promote research studies on the major neurodegenerative diseases of the human brain (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, epilepsy, schizophrenia). The Brain Bank is now well established and is internationally recognised as a unique resource of high quality tissue for research studies in New Zealand and overseas.

PROJECT GRANTS

Role of dorsal raphe in regulating reward prediction by midbrain dopmain neurons

Assoc Prof Brian Hyland

Department of Physiology

University of Otago

$170,000

Patients with Parkinson’s disease, which is mainly a movement disorder, can also suffer from depression. Conversely, patients with severe depression sometimes show slowed movements reminiscent of Parkinson’s disease. These crossover symptoms might reflect interaction of different chemical systems in the brain that are involved in regulating movement and mood. Recently, this research group discovered that the 5-HT, or serotonin system, which is a target for drugs treating depression, displays activity that suggests it could also play a role in controlling the dopamine system, the chemical pathway that degenerates in Parkinson’s disease. In this new study, we will investigate whether the 5-HT system functionally regulates activity in the dopamine system. The results may shed light on why the seemingly disparate disorders of mood and movement can share some symptoms.

Agmatine and age-related cognitive decline: a microdialysis and EM study

Dr Ping Liu, Dr Beulah Leitch, Dr Hu Zhang

Department of Anatomy and Structural Biology

University of Otago

$166,114

Aging leads to cognitive decline and is a major risk factor for Alzheimer’s disease. Agmatine, a metabolite of arginine, is a newly discovered neurotransmitter. We have recently demonstrated that the aging process has dramatic effects on agmatine levels in memory related brain regions and that agmatine supplementation seems to be beneficial for aged rats.

This project aims to understand how the aging process affects agmatine at extracellular and subcellular levels. Knowledge gained from this project will advance our understanding of the mechanisms of brain aging and may lead to the development of agmatine-based therapeutics for cognitive decline during aging.

The Role of Gap Junctions in Ischaemia

Prof Helen Danesh-Meyer, Prof Colin Green, Dr Nathan Kerr

Department of Ophthalmology

University of Auckland,

$95,435

Stroke to the optic nerve results in permanent profound visual loss because of the death of retinal ganglion cells which are the nerve cells of sight. Recent studies show that damage from injured cells passes to healthy neighbouring cells by a process known as bystander mediated cell death. Our research aims to characterize bystander mediated cell death in the retina and to test a new therapy designed to prevent retinal ganglion cell death injury. Limiting bystander cell death could minimize the amount of damage to the nerve cells and consequently preserve vision following injury.

The University of Auckland, Brain Research Centre, Douglas Research Grant administered by the Neurological Foundation

The Role of Chemokines in Directing Progenitor Cell Migration Following Brain Injury

Assoc Prof Bronwen Connor, Renée Gordon

Department of Pharmacology and Clinical Pharmacology

University of Auckland

$183, 066

Neural progenitor cells found in the adult brain may provide an exciting therapeutic strategy for replacing cells lost through brain injury and disease. However, in order to achieve this clinically methods must be developed to direct progenitor cells to migrate to specific areas of cell loss.

One signalling system that may be of importance in this regard is the chemokines and their receptors. This project aims to advance our knowledge regarding the role of chemokines in the adult brain and identify the potential for specific chemokines to direct the migration of neural progenitor cells to areas of brain injury and disease.

KATP channels and survival of nigral dopaminergic neurons during oxidative stress: Neuronal silence may not always be golden.

Prof Janusz Lipski, Dr Ezia Guatteo

Department of Physiology

University of Auckland

$119,817

Parkinson's disease (PD) is defined by classic 'motor' symptoms (tremor in hands, slowness of movements, muscle stiffness, gait disturbances) and its transient responsiveness to a therapy which increases the brain level of dopamine. The motor deficits are mainly due to the loss of dopamine-containing cells located in the region of the brain called the Substantia Nigra.

The cause of cell loss remain uncertain. This study focuses on the group of cell membrane proteins known as KATP channels, which proliferate in the Substantia Nigra. These channels are normally closed, but during metabolic and oxidative stress, they activate in response to a decrease in cellular energy levels. This causes an immediate inhibition of cell electrical activity and, normally, neural protection due to short-term energy conservation. This study will test the hypothesis that prolonged stress activation of KATP channels leads to neural damage, rather than neuro-protection. The study should give new insights into the role of this important group of channels in neural survival, and contribute to development of new therapies of PD based on improved knowledge of the function of KATP channels.

Dendritic Cell Therapy for Glioblastoma Multiforme (GBM)

Dr Martin Hunn

Malaghan Institute of Medical Research

Wellington

$80,000

Glioblastoma multiforme (GBM) is a highly malignant and incurable form of brain cancer. The usual forms of treatment for cancer (surgery, radiotherapy and chemotherapy) are not able to achieve long-term survival. One of the reasons for this may be due to a small group of cells within the tumour (Tumour Stem Cells) that start the tumour but are also very resistant to standard treatments.

One treatment showing promise is immunotherapy, in which the immune system is used to attack the tumour. The PhD aims to firstly to set up a brain tumour laboratory model and then to see whether the results of immunotherapy can be improved by specifically attacking the Tumour Stem Cells. In a related research project, a clinical trial of an immunotherapy in patients with recurrent GBM is about to get underway at Wellington Hospital. Patients will be vaccinated against their own tumour. The second part of this PhD project will involve testing the blood of these patients to determine if the vaccines are effective.

Small Project Grants

The localisation and role of connexins in adult neurogenesis

Dr Simon O’Carroll

Department of Anatomy

University of Auckland

$9,983

The adult brain contains stem cells that differentiate into neurons throughout adult life. These cells migrate to areas of the brain where cells are lost under normal conditions or as a result of disease or injury, offering a powerful tool for cell replacement therapies in neurodegenerative diseases. Connexins, proteins involved in cell-to-cell communication, are involved in the generation and migration of new neurons in the developing brain. This project will study whether connexins also play a similar role in the adult brain. This may ultimately allow us to elucidate a role for connexins in adult neurogenesis.

Longitudinal Investigation of Cortical Thinning in Pre-Symptomatic Huntington’s Disease

Dr Lynette Tippett, Dr Richard Roxburgh

University of Auckland

Auckland

$10,000

Most motor and thinking problems faced by people with Huntington’s Disease (HD) are thought to be caused by damage to the basal ganglia and frontal lobes, regions responsible for movement, decision-making and social behaviour. This research will investigate recent claims that progressive changes in posterior brain areas occur early in the disease and may underlie problems with visual and spatial judgements. In a follow-up study, presymptomatic HD individuals will be reassessed using modern MRI-imaging techniques and thinking tasks sensitive to posterior parts of the brain. Results will enable better understanding of early brain changes in HD, which symptoms develop first and how these symptoms progress.

Dysfunction of Orbitomedial Prefrontal Cortex in Amyotrophic Lateral Sclerosis: An fMRI study

Sandra Meier

Department of Psychology

University of Auckland

$10,000

Amyotrophic Lateral Sclerosis (ALS), the most common form of motor neurone disease is a devastating neurodegenerative disease characterized by rapidly progressive paralysis. Recent findings indicate 50% of individuals with ALS also have difficulty with social interactions, emotions and making effective decisions, functions mediated by frontal brain regions. This study will use functional neuroimaging to test whether a crucial frontal region the orbital prefrontal cortex, is dysfunctional in ALS, by examining whether it activates less when ALS patients alter their behaviour after receiving positive and negative rewards. This work will improve understanding of behavioural and neural deficits in ALS, which will have important clinical implications.

Implementing virtual rehabilitation in a primary school setting: A pilot study

Dr Wayne Hing, Shelley Ruhen, Dr Gwyn Lewis

Health and Rehabilitation Research Centre

AUT University

$9,994

Children with cerebral palsy living in rural New Zealand have difficulty accessing comprehensive rehabilitative treatment. The Interactive Virtual Reality Exercise (IREX) system provides a customised programme of exercise-based games that increase enjoyment and compliance. The virtual reality medium reinforces accurate replication of correct movement patterns, thus improving treatment outcomes and functional abilities. This pilot study will evaluate the feasibility and effectiveness of delivering the IREX system to children with cerebral palsy in a rural school setting. If successful, the study will identify a novel method to administer movement rehabilitation interventions in rural New Zealand.

Identifying novel anti-addiction compounds

Dr Bronwyn Kivell, Aashish Morani

School of Biological Sciences

Victoria, University of Wellington

Identifying novel anti-addiction compounds

$9,850

Drug addiction is a brain disease resulting in devastating consequences to society. Although there are some therapeutic drugs, none are available to treat methamphetamine, cocaine, or amphetamine addiction. Previous research has show that drugs activating a protein called the kappa opioid receptor reduce drug use. Unfortunately, side-effects prevent its therapeutic use. The aim of this project is to measure the anti-addiction effects of a structurally new class of compound known to activate this protein. New compounds with anti-addiction properties will be identified in this study. If these compounds show reduced side-effects, successful anti-addiction therapeutics can be developed in future.

ENDS

Neurological Foundation Fact Sheet

The Neurological Foundation is a charitable trust that raises money for neurological research in New Zealand. Each year it awards more than $1.6 million in grants to New Zealand’s neuroscientists.

The Foundation receives no government assistance and is almost totally funded by the generosity of individual New Zealanders, with more than 98 per cent of contributions coming from donations and bequests.

The funds are capitalised and the interest is used to fund research grants. This system provides ongoing funding for career scientists and long-term research projects. All grant applications are internationally peer-reviewed to ensure only good-quality research is funded.

Since its inception, the Foundation has funded hundreds of projects and currently supports more than 40 research projects being run at tertiary institutions throughout the country.

This unique dedicated funding body has helped New Zealand produce world-class neuroscientists and research. It also uses the combined expertise and detailed knowledge of this group to help keep the public informed of the advances made in neurological disorder prevention and cures.

A full list of previous research project is available on its website.

The Neurological Foundation Annual Appeal runs from Sunday July 5 to Saturday July 11, 2009, and is supported by Mitre 10. Every dollar raised goes into research to ensure a better future for thousands of New Zealanders. Every household will receive an appeal envelope, or individuals can donate online through www.neurological.org.nz

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