Neurological Foundation Announces December 2013 Grant Round

PRESS RELEASE

For immediate release: 16 December 2013

Neurological Foundation Announces December 2013 Grant Round Recipients
$1.2 million committed to neurological research across New Zealand

The Neurological Foundation is pleased to announce that funding of $1,200,000 for neurological research, three postgraduate scholarships, a postdoctoral fellowship, two summer studentships and travel grants has been approved in its December 2013 grant round. The Neurological Foundation is the primary non-government sponsor of neurological research in New Zealand.

Neurological Foundation Executive Director Max Ritchie says “It is exciting to see a mix of basic biomedical research projects and patient-focused clinical studies in this grant round. The ultimate goal of all neurological research is to contribute to major advances in prevention or treatment strategies for patients with brain disorders. The breadth of research in this round will greatly contribute to these advances, and a number of projects will quickly improve patient care. ”

The December grants allocated include the funding of the following projects which will be carried out at the University of Auckland, Victoria University of Wellington, the Malaghan Institute of Medical Research in Wellington, the New Zealand Brain Research Institute in Christchurch and the University of Otago:

• The study of cell function in stroke recovery
• The evaluation of underlying causes of profound swallowing impairments in patients with brain disorders such as stroke and Parkinson’s disease
• The development of a model for future research in Huntington’s disease
• The effect of high-dose vitamin C on brain tumour progression: stage II
• Brain function involvement in paediatric lazy eye
• HARTS: Hand and Arm Recovery Trajectory after Stroke
• The potential of a new class of drug for brain disorders
• New Zealand-led drug trials for new-onset epilepsy

In addition to the above projects, four emerging young neuroscientists have been awarded educational grants to further their careers. Ms Mandana Ghodratipour has been named the inaugural Neurological Foundation Gillespie Postgraduate Scholar. An annual scholarship award, it is named for Peter and Wendy Gillespie, supporters of the Neurological Foundation who are dedicated to endowing bright young New Zealanders into a neurological research career.

All grant details follow.

The Neurological Foundation is an independent body and charitable trust and its funding has facilitated many of New Zealand’s top neuroscientists’ pioneering breakthroughs. Without the ongoing support of individual New Zealanders, the Foundation could not commit to progressing research to the high level that it does. The Neurological Foundation receives no government funding.

www.neurological.org.nz

Neurological Foundation research approved December 2013

Grants totalling $1,200,000 were approved by the Neurological Foundation Council on 6 December 2013.

The Inaugural 2013 Neurological Foundation Gillespie Postgraduate Scholarship

Mandana Ghodratipour
Centre for Brain Research
University of Auckland

Supervisor: Associate Professor Bronwen Connor

Use of direct reprogramming to model Huntington’s disease

The Neurological Foundation’s first Gillespie Postgraduate Scholar, Ms Ghodratipour is fascinated by the topic of cell reprogramming (the process of transforming a particular cell type into a different cell type), and its applications for the study of Huntington’s disease (HD).

HD is a genetic neurological disorder characterised by progressive loss of specific brain cells with devastating neurological consequences. The molecular mechanisms that drive cell death in HD are poorly understood, and as a consequence current therapies only alleviate some clinical symptoms and no cure is available. This project aims to establish a new platform for studying HD by reprogramming skin cells obtained from HD patients directly into the brain cells that are lost in the disease. This cell model of HD will provide a critical disease-specific tool for understanding the disorder at a molecular and cellular level. The long-term aim is to use the model to develop treatments for HD.

2013 Neurological Foundation W & B Miller Postgraduate Scholarships

Tania Fowke
Department of Physiology
University of Auckland

Supervisor: Dr Justin Dean

The role of hylauronan and perineuronal nets in preterm brain injury

Ms Tania Fowke has a particular interest in the developmental and cognitive impairments which occur following preterm brain injury and potential treatments for these deficits.

Despite increased survival of preterm babies with improved hospital care, they exhibit high rates of learning/memory problems in later life. Evidence suggests these deficits are partly caused by impaired growth of neuronal cell branches resulting from low blood flow to the brain (ischemia). However, how ischemia affects neuronal development is not known. There is evidence that neurons produce specialised structures called perineuronal nets (PNNs), which are important for neuronal development. Ms Fowke will determine whether preterm ischemia causes disruption to these structures, and the mechanisms by which this may alter neuronal growth and function. This will help in understanding the causes of cognitive deficits affecting preterm infants.

Amy McCaughey-Chapman
Centre for Brain Research
University of Auckland
Supervisors: Associate Professor Bronwen Connor and Associate Professor John Reynolds

Optimising the transplantation of induced neural precursor cells for Parkinson’s disease

Ms Amy McCaughey-Chapman moved from France with her family six years ago. She completed her final two years of high school in New Zealand and furthered her interest in mathematics and science. She fell in love with the brain sitting in her first-year lectures at the University of Auckland when Professor Richard Faull took her class through the exciting journey of human brain anatomy. Ms McCaughey-Chapman has since mapped out her career desires which include developing her research interests in somatic cell reprogramming and effective drug development for neurodegenerative diseases.

Ms McCaughey-Chapman will progress an exciting research area in Associate Professor Bronwen Connor’s human brain stem cell laboratory, with a focus on a Parkinson’s disease model. Parkinson’s disease (PD) is a movement disorder caused by the death of dopamine cells in the brain. Scientists globally have investigated the transplantation of dopamine-producing cells into PD patients’ brains. Associate Professor’s laboratory recently made worldwide news headlines with ground-breaking research that demonstrated the ability to generate immature dopamine neurons directly from adult human skin; a strategy called direct reprogramming. This strategy has the potential to generate dopamine cells from the patient’s own skin for brain cell replacement. Ms McCaughey-Chapman’s project aims to optimise the transplantation of directly reprogrammed dopaminergic neurons using a model of PD with future therapeutic applications in mind.

2013 Neurological Foundation Philip Wrightson Postdoctoral Fellowship

Dr Tracy Melzer
New Zealand Brain Research Institute and
Department of Medicine, University of Otago, Christchurch
Supervisor: Dr Tim Anderson

Mapping cognitive decline in Parkinson’s disease using MRI scanning.

Dr Tracy Melzer’s research interests centre on the use of Magnetic Resonance Imaging (MRI) techniques to increase science’s understanding of neurological conditions. During his PhD, he developed and employed a number of analysis techniques to investigate cognition in Parkinson's disease using MRI. As a postdoctoral fellow and the MRI research manager at the New Zealand Brain Research Institute in Christchurch, Dr Melzer has had the opportunity to extend this work to investigate brain development and other neurological conditions in addition to Parkinson's disease.

Dementia in Parkinson’s disease (PD), occurring in 80 per cent of patients, is by far the most burdensome aspect of this common neurodegenerative disorder. Therapies to slow down or stop the disease process are being rigorously pursued worldwide, but to assess the effectiveness of these new treatments, we need measures - or to use the more scientific term ‘markers’ - to determine changes in the brain associated with worsening cognitive impairments. Such markers would also assist with patient selection for early intervention clinical trials and improve patient outcomes.

As the 2013 Neurological Foundation Philip Wrightson Postdoctoral Fellow, Dr Tracy Melzer will use advanced brain scanning techniques to assess Parkinson’s disease patients who will be scanned at four year intervals. The MRI scanning technology, relatively unexplored in Parkinson’s disease, will help Dr Melzer to determine the functional state of the brain across the cognitive spectrum and identify markers so that emerging therapies can be tested.

PROJECT GRANTS

Dr Antonio Beretta
Department of Anatomy
University of Otago

$159,106

Astrocytic influence on neuronal GABAA receptor subunits during neuronal development and after injury

Recovery from stroke is difficult and often lifelong. Fortunately, significant neurological and functional recovery does occur after stroke, and research has focused on enhancing this process with the aim of developing improved rehabilitative therapies and drug treatments. Research in the last two decades has shown that astrocytes (the brain’s support cells) play a central role in the functions of neurons. However, it is not clear what effect astrocytes have in recovery from stroke. The aim of this project is to assess whether these cells can influence a neuronal receptor called GABAA, which has a significant role in post-stroke recovery. This assessment will help to develop a detailed understanding of how astrocytes contribute to limiting the spread of damage and facilitating recovery in the brain after stroke.

Dr Maggie-Lee Huckabee
New Zealand Brain Research Institute
Christchurch

$82,650

Incidence, aetiology, and pathophysiology of pharyngeal mis-sequencing in dysphagic
patients with neurologic impairment

Recent clinical experience has identified a patient group with a previously unrecognised cause of profound swallowing impairment (dysphagia) in certain brain disorders such stroke and Parkinson’s disease. These patients mis-sequence their swallowing, causing food or liquid to be misdirected either out the nose or into the airway, instead of directly to the stomach. Some of these patients are unable to eat food safely, requiring tube feeding for nutrition. Dr Huckabee will evaluate the aetiology (cause or origin) of this impairment in a broad group of patients with brain disorders. Results will assist clinicians in accurate diagnosis and treatment, and significantly improve the quality of life in this group of patients.

Professor Louise Nicholson
Centre for Brain Research
University of Auckland

$12,000

A model for intervention in Huntington’s disease

Huntington’s disease (HD) is a devastating genetic neurological disorder which results in the death of specific cells in a part of the brain called the caudate nucleus. Very close by lie the lateral ventricles whose subventricular lining produces new brain cells. Thus there is potential for these new cells to be directed to replace the damaged cells in the caudate nucleus of patient with HD. Professor Nicholson has recently identified a new receptor in human HD brains which may be involved in this process and the aim of this project is to see if these results are replicated in an animal model of HD.  This animal model could then be used for functional studies leading to identification of intervention strategies to halt the progression of this devastating disease.

Dr Patries Herst
Malaghan Institute of Medical Research
Wellington

$10,588

Effect of high dose ascorbate and radiation on tumour progression in an orthotopic mouse
model: stage II

Patients with glioblastoma multiforme (GBM) brain tumours have a very poor prognosis because these aggressive cancers are extremely resistant to radiation therapy. Dr Herst’s laboratory has shown that high dose vitamin C may make GBM cells more sensitive to radiation. However, initial intracranial mouse experiments using daily ascorbate injections with a single dose of radiation did not validate these findings. This stage II study will investigate the use of three doses of radiation each preceded by a single dose of ascorbate to more precisely determine whether high dose ascorbate makes brain tumours more sensitive to, or protects them from, radiation damage.

Dr Benjamin Thompson
Department of Optometry and Vision Science
University of Auckland

$11,999

Understanding and treating deprivation amblyopia

A childhood cataract can cause the brain to process information from the eyes incorrectly, resulting in a loss of vision that persists after the cataract is removed. This loss of vision is known as deprivation amblyopia (lazy eye). In this project, Dr Thompson aims to determine the changes within the brain that cause deprivation amblyopia and to test a new treatment that may improve vision in children with this problem. If this treatment is effective, the principle on which it is based may be relevant to a range of neurological conditions in which healthy brain cells have been deprived of input.

Dr Cathy Stinear
Brain Recovery Clinic
University of Auckland

$133,232

HARTS: Hand and Arm Recovery Trajectory after Stroke

Stroke is a leading cause of disability and currently affects more than 45,000 New Zealanders. Recovering hand and arm function is essential for regaining independence in activities of daily living, and being able to return to work and family roles. The rate of recovery is greatest within the first three months after stroke, but little is known about the longer-term recovery trajectory. This project will be the first to characterise recovery of hand and arm movement in patients from the time of stroke until two years post-stroke. Dr Stinear’s project will determine if the level of impairment at three months post-stroke can predict whether recovery long-term will reflect a virtuous circle of improvement or a vicious circle of deterioration. This knowledge can then be used to decide whether an individual patient has further potential to benefit from therapy two years or more post-stroke.

Dr Darren Day
School of Biological Sciences
Victoria University of Wellington

$12,000

Aptamers as novel therapeutics for treating neurological disorders: Aptamers as SSRIs

Aptamers are synthetic DNA molecules that can be ‘evolved’ in the laboratory to bind to organic or inorganic molecules with high specificity, in a similar manner to antibodies. Aptamers represent a new class of modern pharmaceuticals whose potential as human therapeutics is only just being tapped into. In this study, Dr Day and his team plan to provide proof-of-concept that aptamers can be evolved to bind to neurotransmitter receptors and transporters in the brain, by making an aptamer act as an antidepressant drug that works in a similar manner to drugs such as Prozac (SSRI’s).

Dr Trecia Wouldes
Department of Psychological Medicine
Unviersity of Auckland

$108,250

Prenatal methamphetamine exposure and executive function in childhood

Methamphetamine or “P” use during pregnancy is a serious public health problem in New Zealand. The Infant Development, Environment and Lifestyle (IDEAL) Study is the only prospective, longitudinal study worldwide of prenatal methamphetamine exposure and child outcomes, and comprises four US sites and one in New Zealand. This project will implement Phase II of the New Zealand IDEAL study, a follow-up at 6.5 years of age, and will examine the behaviour and development of 110 children exposed to methamphetamine prenatally and a cohort of comparison children early in their formal schooling. This study could lead to the early identification of children most at risk of ongoing health problems, poor educational achievement and neurological disorders that have been linked to parental substance abuse. These disorders include ADHD, conduct disorder and substance abuse disorder.

Dr Peter Bergin
Neurology Department
Auckland City Hospital

$157,686

In the July 2009 grant round, the Neurological Foundation approved funding for Dr Peter Bergin’s international collaborative pilot study which set up an internet-based platform to recruit patients for epilepsy drug trials. The platform, called EpiNet, can be accessed by adult and paediatric neurologists from anywhere in the world.

In the July 2011 grant round, the Neurological Foundation approved funding for a second study phase to enable an international collaboration of epileptologists to validate both the EpiNet study group and the EpiNet platform before undertaking clinical trials.

Randomised controlled trials of patients with new onset epilepsy; EpiNet-First

This study encompasses a series of four randomised controlled trials (EpiNet-First trials) to determine which of several widely used anti-epileptic drugs (levetiracetam, carbamazepine, lamotrigine and sodium valproate) is most effective as monotherapy (one treatment, vs polytherapy which involves multiple drugs) in patients with recently diagnosed and previously untreated epilepsy. The primary endpoint will be 12 continuous months free from seizures. The trials will be conducted using EpiNet and will involve several New Zealand clinicians as well as neurologists from around the world.

ENDS

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