Neurological Foundation December 2015 Grant Round Recipients

PRESS RELEASE

For immediate release: 7 December 2015

Neurological Foundation Announces December 2015 Grant Round Recipients

Over $1.1 million committed to neurological research across New Zealand

The Neurological Foundation is pleased to announce that funding $1,123,989 for neurological research projects, three postgraduate scholarships, two postdoctoral fellowships, three summer studentships and educational travel grants has been approved in its December 2015 grant round. The Neurological Foundation is the primary non-government sponsor of neurological research in New Zealand.

Neurological Foundation Executive Director Max Ritchie says this grant round showcases the breadth of emerging talent working towards better patient outcomes in New Zealand’s world-class neurological research environment.

“The Foundation received a record number of applications from young investigators applying for fellowship and scholarship grants in this round. And the majority of research grants were awarded to innovative, high-quality projects submitted by emerging scientists at universities and research institutions across the country. Our established research leaders who have received funding support from the Foundation during their careers are now fostering the next generation of talent.”

One of these emerging scientists is Dr Rebekah Blakemore, based at the University of Otago, Christchurch, who has been awarded $144,817 to determine the processes involved in the suppression of voluntary tremors in Parkinson’s disease. The Neurological Foundation awarded the 2015 Repatriation Fellowship to Dr Blakemore in the December 2014 grant round, enabling her to return from her post in Geneva to continue her movement-focused research work with Parkinson’s disease patients under the guidance of Christchurch-based neurologist Professor Tim Anderson. Once her repatriation fellowship is completed in March 2016, Dr Blakemore will begin this project, investigating a patient-focused therapeutic approach with Parkinson’s disease patients in Professor Anderson’s clinic.

Ms Ruth Monk has been awarded the Neurological Foundation Gillespie Postgraduate Scholarship and will work under the supervision of New Zealand’s leading human brain stem cell researcher, Associate Professor Bronwen Connor, in her University of Auckland Neural Reprogramming and Repair laboratory. Ms Monk’s research will use a breakthrough technique recently advanced by Associate Professor Connor to develop a cell model of Huntington’s Disease (HD) by reprogramming skin cells from patients with HD into the specific brain cell type lost in this condition. This model will be used to study the processes involved in cell death and to investigate underlying disease mechanisms such as inflammation and oxidative stress.

Details of all grants awarded continue overleaf.

The Neurological Foundation is an independent body and charitable trust and its funding has facilitated many of New Zealand’s top neurological researchers’ 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.

NEUROLOGICAL FOUNDATION RESEARCH APPROVED DECEMBER 2015

Grants totalling $1,123,989 were approved by the Neurological Foundation Council on 4 December 2015.

Educational travel grants were awarded in addition to the below.

NEUROLOGICAL FOUNDATION PHILIP WRIGHTSON POSTDOCTORAL FELLOWSHIPS

For researchers who have completed a PhD and wish to develop their research careers. This work can be undertaken at either New Zealand or overseas universities or hospitals.

Hayley MacDonald

School of Sports, Exercise and Rehabilitation Science

University of Auckland

$156,484

Ms MacDonald will undertake her Neurological Foundation Philip Wrightson Postdoctoral Fellowship at the University of Birmingham, United Kingdom, and will be supervised by Dr Ned Jenkinson. Dr Jenkinson has spent his career investigating how the brain controls movement, and has extensive research experience in positions at Vanderbilt University in the United States and at the University of Oxford.

Following the completion of her fellowship Ms MacDonald plans to return to New Zealand and integrate the skills and knowledge gained overseas with her current experience, to advance her research career in clinical neuroscience.

Memory encoding and beta de-synchronisation in Parkinson’s disease

Does excessive brain activity contribute to memory deficits in Parkinson’s disease?

Although Parkinson’s disease (PD) is a movement disorder, there is increasing awareness of

significant non-motor (non-movement) burdens experienced by patients. Excessively synchronised brain activity is linked to some motor symptoms of PD, however less is known about how this brain activity contributes to the non-motor symptoms. This project aims to shed new light on the relationship between hyper-synchronised brain activity and the memory deficits experienced in PD. Establishing that such a relationship exists will not only increase our understanding of the neurobiology underpinning PD symptoms, but will pave the way to addressing memory deficits by applying techniques shown to normalise brain activity.

Betty Kao

Cell and Gene Therapy Group

Murdoch Children’s Research Institute

Royal Children’s Hospital, Victoria

$156,484

Ms Kao will undertake her Neurological Foundation Philip Wrightson Postdoctoral Fellowship at the Royal Holloway, University of London in the United Kingdom. Ms Kao will be supervised by Professor George Dickson, who holds a Chair in Molecular Cell Biology and has spent most of his career studying neuromuscular disease and muscle cell biology. Following the completion of her fellowship Ms Kao aims to return to New Zealand and become a principal investigator of her own research group.

An investigation into the role of Rpl3l and regulation of ribosome biogenesis in the

pathogenesis of Duchenne muscular dystrophy: implications for novel therapeutic strategies

Investigating the role of a protein called Rpl3l in the muscular changes of a Muscular Dystrophy model: a new treatment target may be identified

Duchenne muscular dystrophy (DMD) is the most common fatal genetic disorder in

childhood. It is caused by mutations in a gene called DMD that result in the absence of an important structural protein in muscle, called dystrophin. Absence of dystrophin results in progressive muscle weakness caused by pathological changes at the molecular level that are as yet poorly understood. A recent study revealed a protein called ‘Rpl3l’ may play a role in the pathological changes associated with DMD. Ms Kao’s fellowship aims to elucidate the role of Rpl3l in DMD and speculates that it could be targeted as a treatment for this devastating disease.

NEUROLOGICAL FOUNDATION POSTGRADUATE SCHOLARSHIPS

For students who have already completed an Honours or Masters degree to allow them to undertake a PhD course at a New Zealand university.

Neurological Foundation Gillespie Postgraduate Scholarship

Ruth Monk

Department of Pharmacology and Clinical Pharmacology

University of Auckland

$104,095

Modelling Huntington’s Disease: Using direct cell reprogramming to study the

mechanisms underlying a complex genetic neurodegenerative disorder

Creating a model of Huntington’s disease from patient skin cells to further understand the underlying mechanisms and cell death involved in this disorder

Huntington’s Disease (HD) is a highly debilitating genetic neurodegenerative disorder which is characterised by the progressive loss of specific brain cells. What drives this specific cell loss remains largely unknown, and consequently there is no treatment for this disease. Ms Monk’s project aims to generate a model of HD by reprogramming skin cells from patients into the specific brain cell type lost in this condition. This model will provide a novel platform for elucidating the complex mechanisms contributing to brain cell death, and will play an important role in the development of treatments for HD.

Neurological Foundation W & B Miller Postgraduate Scholarships

Molly Swanson

Department of Anatomy with Radiology

University of Auckland

$104,095

Investigating inflammation in the Alzheimer’s Disease Olfactory Bulb

Investigating early inflammatory changes and their influences in the progression of Alzheimer’s Disease

While the most widely known symptom of Alzheimer’s disease (AD) is short term memory

loss, one of the earliest symptoms is often a loss of the sense of smell. This symptom, known as anosmia, is thought to be due to olfactory neuron degeneration or insufficient replacement of olfactory neurons throughout life. Ms Swanson’s research will test the hypothesis that AD pathology is triggered by inflammatory processes in the olfactory bulb by studying post-mortem human brain tissue from the Neurological Foundation Human Brain Bank and using cultured cells. Ultimately, this research will provide insight into early changes occurring in the AD brain which will aid early detection and therapeutic intervention.

Matthew Rowe

School of Biological Sciences

Victoria University of Wellington

$104,095

Inter-cellular mitochondrial transfer: A cell survival mechanism in response to disease and

therapy in neural tissues

The death or survival of brain cells in disease: investigating the biological processes

A striking recent discovery in cell biology is the transfer of mitochondria between cells. Mitochondria are the ‘batteries’ of cells. Mitochondrial transfer has now been shown in a variety of research settings, however the purpose or consequences of this phenomenon are not yet clear. Mr Rowe’s research will examine mitochondrial transfer in two related diseases – neurodegeneration and neurological cancer. Each disease involves the same neural tissues, however the outcomes in each are vastly different - death of the cells in neurodegenerative diseases such as Alzheimer’s, or survival and proliferation of the cells in cancer. This under- explored, likely fundamental biological process has implications for treatment strategies in both neuro-oncology and neurodegeneration.

PROJECT GRANTS

Dr Peter Mace

Department of Biochemistry

University of Otago

$12,000

Structure-function studies of ceroid-lipofuscinosis neuronal protein 5 (CLN5)

How do mutations of a gene affect protein function in the brain and cause Batten disease?

Batten disease is a group of severe childhood neurodegenerative conditions for which there is no known cure. The disease is caused by genetic mutations in one of several different ‘CLN’ genes, including CLN5. However, little is known about the normal function of the protein that is programmed by the CLN5 gene. Dr Mace’s study aims to solve the three-dimensional structure of the CLN5 protein, so as to understand how mutations in the CLN5 gene perturb protein function and cause Batten disease. This may also provide a template for future therapies that directly target the CLN5 protein.

Dr Liana Machado

Department of Psychology

University of Otago

$12,000

Health and Bread Intervention Trial (HABIT): Cognitive Benefits

Does altering the composition of bread improve brain health and reduce the risk of stroke?

Given the prevalence of stroke in New Zealand, stroke prevention is of the utmost

importance. Relatively simple dietary changes have the potential to reduce stroke risk while

simultaneously improving cognitive functioning, and thus quality of life in people otherwise

at higher risk of stroke. Dr Machado’s study will assess the potential cognitive benefits of altering the composition of bread (low salt, beetroot, or hazelnut) consumed by people with at least one marker of metabolic syndrome (for example, having high blood pressure). The findings have the potential to reveal a simple means to improve cognitive health while simultaneously reducing risk of stroke.

Dr Scott Graham

Department of Pharmacology

University of Auckland

$11,500

Assessing RRMS patient sera for soluble blood brain barrier disrupting factors

Does a subset of multiple sclerosis patients have a dysfunction to the barrier protecting the brain?

Relapsing remitting multiple sclerosis (RRMS) is a chronic neurological condition where the

immune system attacks structures in the brain. The disruption to the blood vessels in the brain in the regions where the lesions form is a key feature of multiple sclerosis pathology. Dr Graham’s research aims to investigate whether RRMS patients have soluble factors circulating in their blood that can directly cause disruption to the special vascular structure known as the blood brain barrier (BBB). The BBB protects the brain from foreign substances in the blood that may injure the brain. Identification of these factors will provide an understanding of mechanisms involved in blood brain barrier dysfunction and in the future lead to strategies that directly strengthen the compromised vessels.

Dr Lucia Schweitzer

Department of Biochemistry

University of Otago

$10,448

Characterising the electroencephalogram profiles of Alzheimer’s disease mouse models

Studying brain activity recordings in a mouse model of Alzheimer’s disease to better understand the pathology of the disease

Alzheimer’s disease (AD) is a neurodegenerative disease that presents an immense burden for patients, caregivers and society, with the number of affected individuals rising steadily.

Current mouse models used to study AD do not present the full range of pathology, perhaps

contributing to the lack of a cure or efficient treatment. New research indicates that sleep

patterns and electroencephalograms (EEG) of AD patients differ from the normal population

and that these recordings help diagnose and predict patient outcomes. Dr Schweitzer will use a novel, wireless system to study EEG changes in a newly created mouse model. The results will provide a better understanding of the pathology in these mice, and will provide a baseline data for future tests of therapeutic approaches in both model systems.

Dr Rebekah Blakemore

Department of Medicine

University of Otago, Christchurch

2015 Neurological Foundation Repatriation Fellow

$144,817

Voluntary tremor suppression in Parkinson’s disease

Why can some Parkinson’s disease patients suppress involuntary tremors? Investigating this phenomenon for the first time

Tremor is the most well-known symptom of Parkinson’s disease but unfortunately is not very responsive to the standard pharmacological treatments. Dr Blakemore’s team has, however, encountered a number of patients who are able to temporarily suppress their tremor simply by effort of will. This ability does not appear to be uncommon and is surprising, especially as it has not yet been described in the literature. Dr Blakemore proposes to investigate this phenomenon systematically for the first time, adding functional brain imaging to a suite of movement and muscle measures to understand how people can suppress involuntary tremors.

Dr Louise Parr-Brownlie

Department of Anatomy

University of Otago

$162,047

Do basal ganglia inputs activate motor thalamus neurons?

Investigating the changes in a brain pathway in a model of Parkinson’s disease to improve our understanding of how the brain controls movement

In Parkinson’s disease (PD), loss of the brain chemical dopamine alters activity throughout

movement control pathways. Dr Parr-Brownlie will investigate how one brain pathway, between two parts of the brain known as the basal ganglia and motor thalamus, usually works and if this is altered in PD. Using selective optogenetic stimulation, a cutting-edge technology, Dr Parr-Brownlie will investigate if this connection simultaneously releases two

chemicals, thus is more complex than previously thought. Furthermore, this study will determine if this chemical release is altered in a model of PD. These data will improve our understanding of how the brain controls movement and the changes that occur in PD, thus highlighting new potential treatment sites.

Professor Tim Anderson

Department of Medicine

University of Otago, Christchurch

$146,396

Tau imaging and cognition in Parkinson’s disease

Using new technology to determine how the accumulation of a protein in the brains of Parkinson’s disease patients affects cognitive decline

Most people with Parkinson’s develop cognitive problems and, in many cases, dementia. Suitable objective tools that measure the underlying brain changes that underpin this cognitive decline need to be identified. These tools are important for both trials of new preventative treatments and for use in the clinic. This study will measure accumulation in the brain of an abnormal protein, tau, which is associated with the development of Parkinson’s dementia. Professor Anderson’s study will involve the use of tau PET scans in 70 people with Parkinson’s disease with varying cognitive problems including dementia to show how tau accumulation in the brain reflects degree of cognitive decline. Positron emission tomography scanning is a diagnostic tool that uses a tracer to illuminate specific proteins or cancer cells.

Dr Megan Wilson

Department of Anatomy

University of Otago

$11,500

Sex-dimorphic brain development and disease: the role a non-coding RNA encoded within

the Anti-Müllerian hormone locus

Shedding light on the nature of neurodevelopmental disorders depending upon the sex of the child

Susceptibility to many common neurological and psychiatric conditions differs and shows a

dramatic sex basis – whether the person is male or female. Formation of the human brain

during foetal development follows a slightly different path depending upon the sex of the

child. These differences arise even before sex-hormones are produced. By determining how

male and female sex impacts on the developing brain we hope to shed light on the nature of

how sex differences to neurodevelopmental disorders arise.

SUMMER STUDENTSHIPS

Niamh Hammond

Department of Medicine

University of Otago, Wellington

$4,000

Recent onset transient or episodic headaches with concerning features: risk prediction,

pre-test probability, and imaging selection

Differentiating patients with headache to identify serious and life-threatening brain bleeds

Episodic headaches are a widely experienced complaint. While the majority are due to benign processes, some headaches can herald serious and lifethreatening diseases. One such cause is a type of brain bleed known as a subarachnoid haemorrhage that can present initially as a ‘sentinel bleed’. This research aims to investigate the proportion of patients presenting with transient headache and concerning features that are later confirmed to have these serious brain bleeds. This information will help to identify these patients so that they receive the appropriate scans and treatment in a timely fashion that reduces potential serious illness.

Olufolakemi (Kemi) Bolarinwa

Department of Biochemistry

University of Otago

$4,000

Does sAPP give neuroprotection through its interaction with BACE 1, the enzyme

involved in the production of the neurotoxic amyloid peptide?

Can the interaction of proteins involved in Alzheimer’s disease produce a protective factor?

Late onset Alzheimer’s disease is a growing social and economic burden worldwide and in

New Zealand. As yet there are no effective therapies or early intervention treatments.

Small soluble aggregates of a peptide are believed to be the toxic species that destroys

neurons and impairs memory in Alzheimer’s disease. This peptide is processed from the same large protein as another protein that by contrast restores memory. This neuroprotective protein may bind and inhibit the enzyme that produces the toxic peptide. This project will explore this interaction for the potential of the development of a therapeutic agent or treatment.

Jill Campbell

Department of Psychological Medicine

University of Auckland

$4,000

Non-epileptic seizures in individuals attending neurological services

Examining non-epileptic seizure patient data to better understand symptoms and provide improve clinical services

Psychogenic non-epileptic seizures (PNES) are movements, behaviour or impaired levels of

consciousness that appear epileptic in nature but often lack underlying pathophysiological

findings, resulting in frequent presentation to hospital settings, misdiagnosis and unnecessary treatments. Though there are no abnormal electrical discharges in the brain, the experience of seizures are real to sufferers, who frequently have no control over these events. The significant distress and daily disruption caused by PNES to patients and their families can be reduced by providing neurologic and psychiatric services better targeting patient’s needs. Key to this is gaining a better understanding of the neurological and psychogenic mechanisms driving PNES. Theses seizures have a high occurrence in hospital settings, with prevalence rates up to 40%. This project aims to assess the frequency of PNES presentations to clinical neurological services at Auckland DHB over a three year period. The symptoms experienced by the patient and any other health concerns will be charted. Potential benefits of the study include gaining a better understanding of symptoms, and providing improved clinical services.

ENDS

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