Research 2016

The MND Research Institute of Australia has awarded $5.07 million for three 3-year fellowships and 33 grants-in-aid, listed in the table below. For more information on a specific project, please click the name of researcher.

Projects commencing in 2016

BETTY LAIDLAW MND RESEARCH GRANT (2016-2018)  
Dr Peter Crouch
University of Melbourne
Betty Laidlaw MND Research Grant Copper malfunction in motor neurone disease: a therapeutic target for sporadic MND
POSTDOCTORAL FELLOWSHIPS (2016-2018)  
Dr Michelle Farrar
University of NSW
Beryl Bayley MND Postdoctoral Fellowship Motor neurone diseases in children and young people – understanding pathophysiology and developing treatment approaches
Dr Fleur Garton
University of QLD
Bill Gole MND Postdoctoral Fellowship Identification of novel genetic loci and pathways associated with ALS through interrogation of multiple integrated genomics data sets
Dr John Lee
University of QLD
MNDRIA Postdoctoral Fellowship The role of C3aR signalling in slowing down the disease progression of MND
     
COLLABORATION GRANTS-IN-AID  
Prof Julian Gold
Neuroscience Trials Australia
Cure for MND Collaboration Initiative Grant Pilot Trial of antiretroviral therapy for ALS
Prof Gilles Guillemin
Macquarie Univesity
Cure for MND Collaboration Initiative Grant New directions for early diagnosis of MND: a large-scale longitudinal analysis of multiple biomarkers to find diagnostic and prognostic “fingerprints”.
Dr Bradley Turner
Florey Institute of Neuroscience & Mental Health
Cure for MND Collaboration Initiative Grant A synergistic approach for treatment of MND using neurotrophic and gene therapy
Dr Peter Crouch
University of Melbourne
Jenny Barr Smith MND Collaboration Grant Drug-specific biomarkers to facilitate clinical translation of CuII(atsm) as a potential therapeutic for MND
A/Prof Tracey Dickson
University of Tasmania
Stanford Family MND Collaboration Grant New transgenic mouse models for determining the role of interneuron dysfunction in MND
 
     
GRANTS-IN-AID    
Dr Vinod Aiyappan
Flinders University
Graham Lang Memorial & Mavis Gallienne MND Research Grants A prospective study to assess the causes and treatment of sleep disordered breathing and respiratory failure in patients with MND
A/Prof Julie Atkin
Macquarie University
Cure for MND Foundation Research Grant DNA damage and neurodegeneration in ALS/MND
Dr Catherine Blizzard
University of Tasmania
MNDRIA Grant-in-aid Investigating synaptic dysfunction in ALS
Prof Roger Chung
Macquarie University
Cure for MND Foundation Research Grant New approaches to plasma biomarker studies in MND/ALS
Dr Nicholas Cole
Macquarie University
Cure for MND Foundation Research Grant Elucidating the Pathogenesis of Sporadic Motor Neurone Disease Using Zebrafish Models
Prof Elizabeth Coulson
University of QLD
MNDRIA Grant-in-aid Regulation of neurotrophin signalling as a treatment for MND
Dr Peter Crouch
University of Melbourne
zo-ee MND Research Grant Proteomic investigation of functional copper deficiency in MND
A/Prof Tracey Dickson
University of Tasmania
Jenny Simko MND Research Grant  A systematic human pathology analysis of interneurons in MND
Dr Archa Fox
University of WA
Rosalind Nicholson MND Research Grant Investigating novel stress responsive structures in MND
Dr Nimeshan Geevasinga
University of Sydney
Peter Stearne Familial MND Research Grant Pathophysiological and diagnostic biomarkers of familial and sporadic amyotrophic lateral sclerosis
A/Prof Robert Henderson
University of QLD CCR
MonSTaR Foundation MND Research Grant Using biomarkers to explore heterogeneity of motor neurone disease
Dr Albert Lee
Macquarie University
MNDRIA Grant-in-aid Identifying mechanisms responsible for ubiquitination of TAR DNA-binding protein 43 (TDP-43) in ALS pathogenesis.
Dr Michael Lee
University of Sydney
MNDRIA Grant-in-aid Dissecting the mechanisms underlying muscle fatigue in ALS using acute and cumulative resistance exercise
A/Prof Guillaume Lessene
Walter & Eliza Hall IMR
Cure for MND Foundation Research Grant Novel Agents to Prevent Neuronal Apoptosis in Motor Neuron Disease
Dr Marco Morsch
Macquarie University
Cure for MND Foundation Research Grant Does the transfer of ALS protein aggregates between motor neurons trigger neurodegeneration?
A/Prof Greg Neely
University of Sydney
MNDRIA Grant-in-aid Conserved regulators of synaptic transmission and MND
A/Prof Peter Noakes
University of QLD
Cure for MND Foundation Research Grant Exploiting the opposing actions of complement receptors C3aR and C5aR1 in the treatment of MND.
Dr Susanna Park
University of Sydney
MND Ice Bucket Challenge Grant In vivo markers of ALS disease activity – linking structure to function
A/Prof Kenneth Rodgers
University of Technology Sydney
Cure for MND Foundation Research Grant Identification of environmental risk factors for sporadic motor neurone disease in Australia
Dr Mary-Louise Rogers
Flinders University
Cure for MND Foundation Research Grant Development of novel Immunogenes to improve growth factor support for motor neurons
Dr Darren Saunders
University of NSW
Neale Daniher MND Research Grant Ubiquitin Depletion as a Cause of Amyotrophic Lateral Sclerosis (ALS).
Dr Sandy Shultz
University of Melbourne
Mick Rodger & Benalla Act to d'feet MND Research Grant Treatment with GSK2606414 in mouse models of motor neurone disease and traumatic brain injury
Dr Frederik Steyn
University of QLD
Cunningham Family MND Research Grant Metabolic and gut dynamics in MND: Identifying novel strategies to meet energy needs in patients
Dr Lachlan Thompson
Florey Institute for Neuroscience & Mental Health
Cure for MND Foundation Research Grant Towards cell-based therapies for MND: identifying and tackling practical challenges in pre-clinical research.
Dr Adam Walker
Macquarie University
Cure for MND Foundation Research Grant Pre-clinical therapeutic testing and biochemical changes associated with neuron survival in a validated TDP-43 mouse model of MND
Dr Kelly Williams
Macquarie University
MNDRIA Grant-in-aid Identification of phenotypic modifiers in sporadic ALS through systems genomics
Dr Shu Yang
Macquarie University
MNDRIA Grant-in-aid Ubiquitin Proteasome System dysfunction as a biomarker for the diagnosis and prognosis of MND
Dr Justin Yerbury
University of Wollongong
Cunningham Family MND Research Grant Development of a biocompatible functionalised liposome drug delivery system to increase efficiency of delivery to motor neurons.


BETTY LAIDLAW MND RESEARCH GRANT (2016 - 2018)

Dr Peter Crouch
University of Melbourne

Copper malfunction in motor neurone disease: a therapeutic target for sporadic MND

We have developed the compound copper-ATSM as a treatment option for MND. Based on our outcomes from testing in animal models of MND and via our partnership with Collaborative Medicinal Development, Phase I clinical testing of the drug (for safety and tolerability) in Australian MND patients is due to start in 2016. As the initial stages of clinical testing commence, this research aims to obtain a better understanding of which drug-related processes fail in MND and when they fail relative to symptom progression. This work will generate the new information that can support further progression of copper-ATSM towards the efficacy stages of clinical testing.
 

POSTDOCTORAL FELLOWSHIPS (2016-2018)

Beryl Bayley MND Postdoctoral Fellowship (2016-2018)

Dr Michelle Farrar
University of New South Wales

Motor neurone diseases in children and young people – understanding pathophysiology and developing treatment approaches

Motor neurone diseases in children and young people are a devastating group of disorders producing significant disability and mortality. This project will combine clinical, functional and specialised nerve assessment strategies to provide a comprehensive evaluation of pathogenesis and progression of MND in children and young people with the aim to develop and validate novel sensitive outcome measures for use in the clinical setting and trials. In addition, the project aims to accelerate clinical translation of potential therapies by further developing clinical trial readiness and assessment of health outcomes for children and young people with MND.

Bill Gole MND Postdoctoral Fellowship (2016-2018)

Dr Fleur Garton
The University of Queensland

Identification of novel genetic loci and pathways associated with ALS through interrogation of multiple integrated genomics data sets

Insights into amyotrophic lateral sclerosis (ALS) have come from studies of the known mutations. However, in >85% of cases, the causative mutation of ALS is not known. In this project, we will use novel genomics and molecular methods to improve diagnosis and enhance the understanding of severe neuronal degeneration. This includes, the characterization of ALS patient neurons (derived from non-invasively collected urine cells) to fast-track genetic discovery with patient-specific treatment assays. We envisage an expanded diagnostic and treatment suite that will provide answers and options for the 85% of ALS patients for whom there is no known genetic cause.

MNDRIA Postdoctoral Fellowship (2016-2018)

Dr John Lee
The University of Queensland

The role of C3aR signalling in slowing down the disease progression of motor neuron disease

In MND, activation of the immune system leads to increased levels of C3aR. Although C3aR is primarily involved in immunity, it also affects energy balance and the production of nutritional factors known to support the nerve cells in the brain and spinal cord. This study will use mouse models of MND and MND patients to investigate whether C3aR can provide energy and support to save nerve cells from death. By identifying a protective role for C3aR in MND, we can determine whether targeting C3aR is a viable therapeutic option for slowing MND in humans.


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COLLABORATION GRANTS-IN-AID

Cure for MND Collaboration Initiative Grant

Prof Julian Gold   
The Albion Centre, Sydney

Pilot trial of antiretroviral therapy for amyotrophic lateral sclerosis

This is a pilot clinical trial, The Lighthouse Project, to test the possibility that a virus may be the cause or trigger for motor neuron disease. The type of virus involved is actually part of our genes and therefore the therapy needs to be very specific. We will be testing an anti-retroviral drug in 30-40 patients with relatively early ALS and treating them for at least six months. There will be centres in Sydney and Melbourne and also in the U.K. This trial is an important step in trying to find the cause of MND and to contribute to our scientific understanding of this disease.


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Cure for MND Collaboration Initiative Grant

Prof Gilles Guillemin     
Macquarie University

New directions for early diagnosis of MND: a large-scale longitudinal analysis of multiple biomarkers to find diagnostic and prognostic “fingerprints”.

This project aims to assess the diagnostic potential of combining markers already identified by Australian and international research groups together with a large number of inflammatory molecules (in total 95 molecules out of 1 mL of serum) as biomarkers for ALS. This will help us develop better diagnostics as well as a more accurate understanding of the onset, triggers, environmental factors and progression of ALS. Moreover, we expect that identifying robust and sensitive sets of biomarkers may provide new hints for novel therapeutic strategies, or at least new directions for research on possible therapies.
 

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Cure for MND Collaboration Initiative Grant

Dr Bradley Turner
Florey Institute of Neuroscience and Mental Health, Melbourne

A synergistic approach for treatment of MND using neurotrophic and gene therapy

MND is a complex and multifactorial disorder that is likely to require multiple agents with synergistic effects targeting different aspects of disease for effective treatment. This novel international collaborative project will examine the efficacy of a combined gene and neurotrophic therapy approach to improve motor neuron health and connections to muscle in preclinical models of MND.  Importantly, these gene and neurotrophic therapy agents can be rapidly adapted to human studies which will accelerate clinical development of this approach if supported for MND.
 

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Jenny Barr Smith MND Collaboration Grant

Dr Peter Crouch
The University of Melbourne

Drug-specific biomarkers to facilitate clinical translation of CuII(atsm) as a potential therapeutic for MND.

Our team has developed a potential treatment option for MND and through our collaboration with a drug development company in the United States have commenced preparations to test the drug in Australian MND patients.  One aspect of these preparations is our development of an analytical technique to monitor the drug’s activity while it is being tested in people with MND.  The research we plan to undertake via funds from the Jenny Barr Smith MND Collaboration Initiative aims to establish clinical utility of this analytical technique.  This type of research is important because it can be used to guide on-going assessment of the drug when it is administered to people with MND

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Stanford Family MND Collaboration Grant 

A/Prof Tracey Dickson     
Menzies Institute of Medical Research, The University of Tasmania

New transgenic mouse models for determining the role of interneuron dysfunction in MND

There is considerable evidence that, in MND, motor neurons may be dying due to a toxicity that is triggered due to their over-activity – known as excitotoxcity. We have new evidence that this toxicity may initially be triggered by the death or dysfunction of another type of neuron in the brain – the interneuron. Interneurons are critical regulators of motor neuron activity and modulators of the balance that is essential for normal brain function.
In this research project, we will make new transgenic mouse models that will allow us to determine if interneuron and inhibitory pathology could in fact be a central mechanism for this devastating disorder. If we are correct, translation to the development of a therapeutic would be rapid, with many modulators of inhibitory function already available for testing.

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GRANTS-IN-AID

Graham Lang Memorial and Mavis Gallienne MND Research Grants

Dr Vinod Aiyappan            
Flinders University, SA

A prospective study to assess the causes and treatment of sleep disordered breathing and respiratory failure in patients with motor neurone disease

Non-invasive ventilation (NIV) provides respiratory support via a mask and machine is the standard care for MND patients who develop sleep symptoms or respiratory failure. But the current NIV treatment uses standard settings in all the patients, which might result in sub-optimal treatment. This project aims to characterize the patterns of abnormal breathing in MND patients and to investigate changes in breathing abnormalities as the disease progresses. We will also test the usefulness of a new “smart” ventilator which can provide more personalised treatment (depending on the underlying breathing abnormality) in MND patients.


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Cure for MND Foundation Research Grant

A/Prof Julie Atkin          
Macquarie University, NSW

DNA damage and neurodegeneration in ALS/MND

Our genes are under constant attack.  Hence cells have developed systems to detect/repair DNA damage, termed the ‘DNA damage response’. However, if DNA cannot be repaired correctly following damage, permanent changes to our genetic information result that ead to motor neuron death. We have identified that damage to DNA is present in cells carrying mutations that cause most genetic forms of motor neuron disease (MND). This project will examine the detailed mechanisms by which this occurs. It will examine whether drugs that inhibit the DNA damage response are protective in cellular models of MND.


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MNDRIA Grant-in-aid

Dr Catherine Blizzard  
The University of Tasmania

Investigating synaptic dysfunction in ALS

The RNA binding protein TDP-43 is likely to play a critical role in ALS. TDP-43 is a major component of the pathology in patients with sporadic disease, and genetic mutations to this protein cause inheritable ALS. We are investigating how TDP-43 is involved in neuronal communication, acting at the synaptic connections between neurons.  We aim to determine how synaptic changes can lead to the neuronal death that happens in ALS, with the hope of pin pointing the earliest changes occurring to identify new targets for therapeutic treatment.


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Cure for MND Foundation Research Grant

Prof Roger Chung    
Macquarie University, NSW

New approaches to plasma biomarker studies in MND/ALS

There is an urgent need to identify a series of biomarkers that can be used to improve the speed of diagnosis, and predict more accurately prognosis and other clinical parameters in ALS.  This project will utilize a new proteomic technology to identify potential protein biomarkers in blood samples from ALS patients. We predict that these biomarkers may be useful in future for improving diagnostic and prognostic clinical evaluations.  These protein biomarkers may identify also novel biological processes associated with disease pathogenesis, and this may lead to new insight into the causes of ALS.


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Cure for MND Foundation Research Grant

Dr Nicholas Cole            
Macquarie University, NSW

Elucidating the pathogenesis of sporadic motor neurone disease using zebrafish models

A complete understanding of the exact cause and a cure for the motor neuron disease Amyotrophic Lateral Sclerosis (ALS) remain elusive. The majority of ALS cases (over 90%) occur sporadically with no known genetic cause or family history. Our aim is to create an animal model that develops genuine ALS-like symptoms so that we can study these animals in the laboratory to understand the biology of the human disease and ultimately find a cure. This will be done in zebrafish, a well-established laboratory research animal for human disease research that are also suitable for the rapid testing of potential new treatments.
 

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MNDRIA Grant-in-aid

Prof Elizabeth Coulson  
The University of Queensland

Regulation of neurotrophin signalling as a treatment for MND

Motor neuron disease is caused by the dysfunction and death of motor neurons, mediated by the death-signalling p75 neurotrophin receptor (p75NTR). We have developed a novel candidate therapeutic, called c29, that can inhibit p75NTR and facilitate growth factor-induced survival signalling in the SOD1 model of motor neuron disease. The aim of the current application is to alter the treatment strategy to provide c29 selectively to motor neurons to provide further proof of principle that this treatment is effective, a key step in the ongoing preclinical development of c29 as a treatment for this devastating disease.

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zo-ee MND Research Grant

Dr Peter Crouch           
The University of Melbourne

Proteomic investigation of functional copper deficiency in MND

Copper is an essential element needed by all forms of life, yet we have discovered that brain and spinal cord tissue collected from people who died of MND does not contain sufficient copper to sustain normal function.  In other words, the parts of the brain and spinal cord affected by MND are functionally copper deficient.  This suggests that limited availability of copper in the brain and spinal cord contributes to the development of MND.  The research we plan to undertake aims to directly address this possibility with the intention to identify new therapeutic opportunity. 

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Jenny Simko MND Research Grant

A/Prof Tracey Dickson
The University of Tasmania

A systematic human pathology analysis of interneurons in MND

In preliminary studies in our laboratory we have discovered that in a subset of MND human brain cases there is a loss of a certain type of neuron known as the interneuron. Not all cases show this loss. In this investigation we will perform systematic pathological analysis in a much larger set of human post-mortem MND tissue, sourced through the Oxford Brain Bank and the Australian Brain Bank Network. This will allow us to determine which types of cases show this specific type of cell loss and importantly our experiments will determine if interneuron pathology precedes, and therefore could be a trigger for, motor neuron pathology and cell death in the brain and/or the spinal cord, causing MND.   


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Rosalind Nicholson MND Research Grant

Dr Archa Fox          
University of Western Australia

Investigating novel stress responsive structures in MND

MND/ALS is linked to toxic protein aggregates in neurons. We have found that the same proteins that aggregate in MND are also needed to form granules such as ‘paraspeckles’ when cells are stressed. The aim of this project is to investigate this useful aggregation into paraspeckles to try to understand the effects on the neurons when this process is altered in MND. Understanding which stresses are critical, and how to help motor neurons cope with the stress is an important step towards understanding what causes MND. 
 

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Peter Stearne Familial MND Research Grant

Dr Nimeshan Geevasinga      
The University of Sydney

Pathophysiological and diagnostic biomarkers of familial and sporadic amyotrophic lateral sclerosis

Familial forms of motor neuron disease (MND) account for around 10-15% of all cases of MND. Our goal is to study the most common form of familial ALS, secondary to the c9orf72 mutation. Our goal is to enrol carriers of this gene mutation and follow them up over time to see how their brain function changes (when measured by a unique magnetic test).  This is in addition to evaluating their overall muscle strength and functional scores. By better understanding, when and how MND may start, we can tailor treatment options more appropriately.


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MonSTaR Foundation MND Research Grant

A/Prof Robert Henderson  
University of Queensland Centre for Clinical Research

Using biomarkers to explore heterogeneity of MND

This project will continue important work examining biomarkers in MND. There is a critical need for reliable biomarkers to assess disease progression and potentially for use in treatment trials. Over the last few years we have been examining blood biomarkers and in particular neurofilaments. In this project, we will categorize those with MND according to genotype, whether or not there is cognitive impairment and rate of survival, and will compare our blood biomarkers in the different groups. We will determine whether the blood biomarkers can be used to distinguish the groups. We hope that will also allow us to provide insight into mechanisms.


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MNDRIA Grant-in-aid

Dr Albert Lee                
Macquarie University, NSW

Identifying mechanisms responsible for ubiquitination of TAR DNA-binding protein 43 (TDP-43) in ALS pathogenesis

The major hallmark of almost all ALS cases is the presence of aggregates of a particular protein (TAR DNA-binding protein 43 (TDP-43. Only a small percentage of these clinical cases bear mutations in the TDP-43 gene, with most representing sporadic disease origins. Our team has recently identified new mutations in a gene that encodes a protein that is directly involved in protein recycling in motor neurons. This project will use a series of experimental techniques to precisely identify the mechanisms by which this novel ALS protein may affect TDP-43 inclusions and map signalling pathways that are impaired in motor neurons.


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MNDRIA Grant-in-aid

Dr Michael Lee               
The University of Sydney

Dissecting the mechanisms underlying muscle fatigue in ALS using acute and cumulative resistance exercise

Fatigue is a common complaint among people with ALS. It can negatively impact on physical activity, leading to sedentary behaviour and disuse atrophy. A better understanding of the mechanism underlying fatigue has significant clinical implications for the management of ALS. In this study, we will examine the effects of exercise-induced fatigue on intracortical inhibition using established transcranial magnetic stimulation (TMS) techniques. Different types fatiguing exercises have been shown to have differential modulatory effects on intracortical inhibition in healthy subjects; however, it is unknown whether they have similar effects in ALS patients. Our study will help to clarify this important issue.


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Cure for MND Foundation Research Grant

A/Prof Guillaume Lessene          
The Walter & Eliza Hall Institute of Medical Research, VIC

Novel agents to prevent neuronal apoptosis in motor neuron disease

MND is characterised by “apoptosis”, a cellular process leading to the death of neurons under physiological stress. Recent advances in understanding how apoptosis works have allowed the development of new drugs that stops neuronal cell death and the progression of MND.
Using our expertise in apoptosis and drug development, we identified the first pharmacological inhibitors of apoptosis. Extending from these studies, we hope to develop new drugs that will provide the basis for clinical trials in MND patients. Our goal is to slow or stop the progression of MND by harnessing the therapeutic potential of apoptosis inhibition.


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Cure for MND Foundation Research Grant

Dr Marco Morsch          
Macquarie University, NSW

Does the transfer of ALS protein aggregates between motor neurons trigger neurodegeneration?

The accumulation of proteins in neurons and glia is a pathological hallmark of many neurodegenerative diseases. Clinical data from MND patients describes a focal onset and the subsequent spread of muscle paralysis to other regions.   This project aims to understand how ALS proteins can transfer from one cell to the next. Our team has established a zebrafish model where we can track the release and spread of ALS-proteins. The outcome of this study will be the first visualisation of ALS-protein transfer in a living animal, and provide greater understanding of whether this represents a potential pathogenic mechanism in ALS.


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MNDRIA Grant-in-aid

A/Prof Greg Neely         
The University of Sydney

Conserved regulators of synaptic transmission and MND

Recent efforts to pinpoint the genetic causes of MND have been difficult for the vast majority of cases, suggesting complimentary approaches are required. Since MND involves defects in nerve transmission, we have combined human genomic data with systematic assessment of motor neuron function to identify 99 new genes that are require for motor neuron transmission in a live animal. Many of these genes can be considered as novel therapeutic targets for MND, and here we continue our efforts to discover and understand genes that can cause or prevent loss of motor neurons. 


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Cure for MND Foundation Research Grant

A/Prof Peter Noakes   
The University of Queensland

Exploiting the opposing actions of complement receptors C3aR and C5aR1 in the treatment of MND

One major part of the immune system is the complement cascade of which C3 and C5 are the key proteins. C3 is broken down into C3a and C3b, and likewise C5 is broken down to C5a and C5b. C3a and C5a activate their receptors C3aR and C5aR1 to produce opposing actions. In the nervous system, C3aR activation can protect nerve cells from death, while C5aR1 activation can drive nerve cell death. We will exploit these two opposing actions of C3aR and C5aR1 to enhance the neuro-protective actions of C3aR within the brain-spinal cord, while at the same time block with our drug the neuro-destructive actions of C5aR1, in animal models of MND. 


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MND Ice Bucket Challenge Grant

Dr Susanna Park          
The University of Sydney

In vivo markers of ALS disease activity – linking structure to function

There remains no sensitive method to diagnose ALS or to determine how quickly the disease will progress. Our study will undertake a longitudinal study of ALS patients using neuroimaging (FDG-PET) and neurophysiological (threshold tracking TMS) tools to determine long term utility in the clinic. FDG-PET is an imaging technique which can examine changes in brain energy use in real time while threshold tracking TMS can determine the excitability level of the brain. Together these techniques provide a powerful and cutting edge assessment of current brain function - important to identify changes associated with disease progression in ALS.


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Cure for MND Foundation Research Grant

A/Prof Kenneth Rodgers 
University of Technology Sydney

Identification of environmental risk factors for sporadic motor neurone disease in Australia

Toxins such as heavy metals, pesticides, fertilisers and exposure to algal blooms have been implicated as causes of sporadic MND (sMND). Long-term exposure to neurotoxins can give rise to clusters or ‘hot-spots’ of sMND. We will map sMND patients in NSW to identify any geographical clusters of sMND. We will then look for neurotoxins in plasma, hair and in the local environment to identify which toxins increase the risk of developing sMND. Limiting exposure to environmental neurotoxins could result in a gradual decline in the incidence of sMND and protect future generations of Australians.


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Cure for MND Foundation Research Grant

Dr Mary-Louise Rogers   
Flinders University. SA

Development of novel immunogenes to improve growth factor support for motor neurons

Lack of growth factor support is one reason motor neurons die in MND. Animal studies have demonstrated the potential of glial cell-derived neurotrophic factor (GDNF), and hepatocyte growth factor (HGF) for MND. We have developed a technology called immunogenes that enable delivery of therapeutic genes into the nerves affected in MND from the circulation. This project will test immunogenes in newborn mice to determine dosing for delivery of GDNF and HGF for future treatments of mice living with MND. Data from this project will answer questions about efficacy of neurotrophic therapy with immunogenes for people living with MND.


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Neale Daniher MND Research Grant

Dr Darren Saunders              
University of New South Wales

Ubiquitin depletion as a cause of ALS

We have identified the ubiquitin system - the cellular recycling and garbage removal system - as a novel therapeutic target for the treatment of MND. A hallmark of MND pathology is the accumulation of aggregates of ubiquitin-tagged proteins within motor neurons. We propose that disrupted ubiquitin balance (leading to cell death) is an underlying cause of MND. We will use stem cell models and transgenic animals to test a novel approach to increasing ubiquitin availability in motor neurons. This will result in a fundamental shift in our understanding of MND pathogenesis, and provide pre-clinical validation of a novel therapeutic target.


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Mick Rodger & Benalla Act to d'feet MND Research Grant

Dr Sandy Shultz              
The University of Melbourne

Treatment with GSK2606414 in mouse models of motor neurone disease and traumatic brain injury

Traumatic brain injury (TBI) has been suggested to increase the risk of motor neuron disease (MND). We found that TBI in rodents causes progressive and degenerative changes - including TDP-43 pathologies - consistent with those occurring in MND, which supports the notion that TBI may be a causal link to MND. A new drug, GSK2606414, mitigates the neurotoxic effects of TDP-43 pathologies. Here we will investigate GSK2606414 treatment in mouse models of MND and/or TBI. These studies will increase our understanding of the causes and mechanisms of MND and TBI, and may identify a novel treatment for these devastating conditions. 


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Cunningham Family MND Research Grant

Dr Frederik Steyn       
The University of Queensland

Metabolic and gut dynamics in MND: Identifying novel strategies to meet energy needs in patients

Energy needs of people living with MND change as their symptoms worsen. We found that the ability of the gut to respond to a meal may be impaired in MND, and thus MND patients may be unable to meet their changing energy needs through diet alone. As part of a larger program, we will investigate the impact of MND, and consequential changes in dietary intake on gut bacteria. Bacteria in our gut help us absorb and regulate energy use. Thus, this project will investigate gut bacteria as a possible future target to slow disease progression through modifying energy use and availability.
 

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Cure for MND Foundation Research Grant

Dr Lachlan Thompson     
Florey Institute for Neuroscience and Mental Health, Melbourne

Towards cell-based therapies for MND: identifying and tackling practical challenges in pre-clinical research

Our laboratory is interested in the idea that stem cells can be used to grow new neurons that can functionally replace those lost in neurodegenerative conditions, such as MND. We have all been hearing for a long time now about the promise of stem cells as treatment option for patients with brain and spinal cord injury. So why aren’t we there yet? This project is aimed at addressing the practical challenges in translating stem cell therapies to the clinical, particularly the need for immune suppression that allows for survival of the stem cell grafts, but without accelerating disease progression.

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Cure for MND Foundation Research Grant

Dr Adam Walker      
Macquarie University, NSW

Pre-clinical therapeutic testing and biochemical changes associated with neuron survival in a validated TDP-43 mouse model of MND

A major hurdle in understanding what causes MND and in developing treatments has been the lack of reliable MND animal models. Recently at the University of Pennsylvania, Dr Walker characterised new genetically modified mice that for the first time develop brain and spinal cord pathology along with progressive movement deficits similar to >97% of MND patients. This project will establish these mice in Australia for pre-clinical testing of potential MND therapies, and will investigate the biochemical changes that cause neurodegeneration in the early stages of MND with the aim of identifying new therapeutic targets. 

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MNDRIA Grant-in-aid

Dr Kelly Williams              
 Macquarie University, NSW

Identification of phenotypic modifiers in sporadic ALS through systems genomics

Sporadic ALS comprises the vast majority of all ALS cases, however little is known about the underlying cause. There is compelling evidence for a genetic contribution, yet we observe significant variation in terms of patient age and site of onset, disease progression, prognosis and response to treatment, suggesting the existence of molecular modifiers acting to control how ALS manifests. These molecular modifiers include genetic variation (DNA genotype), physical changes to DNA (DNA methylation), and expression of genes (RNA expression). We will investigate how these molecular modifiers correspond with, or influence one another and whether they are playing a causal role in sporadic ALS. 

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MNDRIA Grant-in-aid

Dr Shu Yang                         
Macquarie University, NSW

Ubiquitin Proteasome System dysfunction as a biomarker 

for the diagnosis and prognosis of MND
The existing tools for diagnosing and monitoring MND disease progression are poor. The aim of this study is to investigate the possibility of using MND patients’ fibroblast cells as a platform to facilitate diagnosis and prognosis. Through a cell-based assay, we found that protein degradation was inefficient in MND patients’ cells as in unaffected individuals. We are now examining protein degradation in a larger cohort of MND patients’ fibroblasts and also looking for changes with disease progression in these cells. This will serve as a pilot study for the development of a new rapid diagnostic tool, which may be translated for further testing in MND clinics.

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Cunningham Family MND Research Grant

Dr Justin Yerbury       
Illawarra Health and Medical Research Institute
University of Wollongong, NSW

Development of a biocompatible functionalised liposome drug delivery system to increase efficiency of delivery to motor neurons

Currently there is no effective therapy for the treatment of MND. One of the main hurdles to the development of new drugs is achieving an efficient delivery of the drugs to the location in the brain and spinal cord where it is required. Our objective is to develop a therapeutic delivery system that will increase the success rate of targeting any drug to motor neurons in the brain and spinal cord. This will have a major impact on the types of drugs that can be delivered to motor neurons, opening up many new potential avenues of therapy for MND.

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NHMRC/MNDRIA Co-funded Postgraduate Award 2016 - 2017

Dr Nidhi Garg
Brain and Mind Centre, University of Sydney, NSW

Clinical phenotypes and novel neurophysiological and immunological biomarkers in inflammatory neuropathy

The aim of the project is to gain a better understanding of inflammatory and degenerative neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and motor neurone disease (MND). At times it can be difficult to differentiate immune-mediated motor neuropathies from MND. The identification of specific antibody markers and neurophysiological parameters will aid in diagnosis of inflammatory neuropathies and differentiation from motor degenerative disorders such as MND. While we have treatment available for the inflammatory neuropathies (such as intravenous immunoglobulin or IVIg), no such treatment is yet available for patients with MND. Identification of novel biomarkers will allow for more accurate diagnosis, prognostication and better treatment planning for patients.

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MNDRIA PhD Top-up Grant 2016 - 2018

Dr Thanuja Dharmadasa
Brain and Mind Centre, University of Sydney, NSW

Motor Neurone Disease: site of origin and patterns of disease spread

Motor neurone disorders (MND) are one of the most rapidly-progressive age-related diseases known to man. However, the poorly understood disease factors limit the development of adequate treatments. This clinical study will use examination findings, nerve studies, brain imaging and genetic testing totry and differentiate the various subtypes of MND, develop markers of disease, and to identify the site of onset and the spread of disease. The goal of this clinical research will be to enable an early diagnosis, improve patient assessment and management, and provide new knowledge regarding nerve function in these patients. This overall insight will hopefully be able to advance the development of new treatment strategies.

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MNDRIA PhD Top-up Grant 2016 - 2018

Emily McCann
Macquarie University, NSW

Investigating the genetic and epigenetic basis of amyotrophic lateral sclerosis

There is currently no cure or effective treatment for MND, and genetic mutations are the only proven cause. Approximately 10% of MND is hereditary, and only two thirds of these cases are accounted for by known genetic mutations, leaving the cause of most MND unsolved. We aim to uncover further genetic variants and patterns of DNA chemical modifiers (epigenetic markers) that underlie MND by interrogating samples from MND patients and their families. Identifying such signatures of MND will provide greater insight into the molecular physiological processes underlying disease. As such, our research has great potential to identify targets for future MND therapeutics, particularly epigenetic markers that are reversible and targeted by many currently available drugs.


Susie Harris Travel Fellowship 2016 

Dr Rebekah Ahmed
Brain and Mind Centre, University of Sydney, NSW

Eating behaviour and cognition in the ALS-FTD spectrum: effect on survival 

This grant will allow Rebekah to work with collaborators at the Institute of Metabolic Sciences, Cambridge, UK, and to present the findings of her work at the International ALS/MND Symposium in Dublin, Ireland, in December 2016.

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Jenny and Graham Lang Collaboration Travel Grant 2016

Dr Frederik Steyn
Faculty of Medicine and Biosciences, University of Queensland

Re-evaluation of hypermetabolism and the assessment of endogenous adipose as a modifier of ALS/MND progression

This grant will assist visits to the laboratories of Professor Leonard van den Berg in the Netherlands and Professor Pierre-Francois Pradat in France. The award will strengthen and expand research to help define patients most likely to benefit from metabolic-directed therapies.
 

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Projects continuing in 2016

MND Australia Leadership Grant 2013 - 2016

Associate Professor Ian Blair
Australian School of Advanced Medicine, Macquarie University, NSW

Investigating the pathogenic basis of familial MND 
MND Australia Ice Bucket Challenge Grant 2015 - 2017

Professor Naomi Wray
Queensland Brain Institute, University of Queensland

Sporadic ALS Australian Systems Genomics Consortium (SALSA-SGC) 
  Bill Gole MND Postdoctoral Fellowship 2014 - 2016

Dr Jacqueline Leung
Wicking Dementia Research and Education Centre, University of Tasmania

Investigating the role of oligodendrocytes in ALS 
Bill Gole MND Postdoctoral Fellowship 2015 - 2017

Dr James Howells
BMRI, University of Sydney, NSW

Investigating the role of oligodendrocytes in ALS 

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Beryl Bayley Postdoctoral MND Research Fellowship 2015 - 2017

Dr Parvathi Menon
Westmead Hospital, University of Sydney, NSW

Insights into ALS pathophysiology from patterns of disease progression 

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NHMRC/MNDRIA Co-funded Postgraduate Scholarship

Nicole Sheers
Institute of Breathing and Sleep, Austin Health, VIC

Lung volume recruitment in neuromuscular disease: Can ‘breath-stacking’ improve lung function, respiratory symptoms and quality of life for people with neuromuscular disease?

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MNDRIA PhD Scholarship Top-up Grant

Victoria McLeod
I
HMRI, Florey Institute, VIC

Androgen Receptor Dysregulation in ALS

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MNDRIA PhD Scholarship Top-up Grant

Dr Rebekah Ahmed
Neuroscience Research Australia, NSW

Eating, autonomic and sexual dysfunction in motor neuron disease and frontotemporal dementia