Motor Neurone Disease

Understanding, preventing and treating motor neurone disease (MND)
We strive to understand the mechanisms behind a range of neurological conditions including motor neurone disease, to improve diagnosis and develop new treatment strategies.

About our research

The Brain and Mind Centre’s Motor Neurone Disease and Neurodegenerative & Neuromuscular Diseases Groups are multidisciplinary teams of clinicians, scientists, biomedical engineers, doctoral and postdoctoral students led by Professor Matthew Kiernan and Professor Steve Vucic.

Our teams collaborate to understand the mechanisms behind neurological conditions such as motor neurone disease and seek to develop novel diagnostic tools and new treatments for these conditions.

Our current projects

Professor Matthew Kiernan leads a program of research currently investigating mechanisms, biomarkers and possible prevention strategies for neurodegeneration in motor neurone disease, frontotemporal dementia, chemotherapy-induced neurotoxicity, stroke, Machado-Joseph disease, spinal muscular atrophy and other inherited neuropathies.

Furthermore, the Motor Neurone Disease Group conduct clinical trials through the ForeFront Clinic to investigate potential drug treatments for motor neurone disease and chronic inflammatory demyelinating polyneuropathy (gradually increasing sensory loss and weakness associated with loss of reflexes). The research is fully integrated with the ForeFront Clinic, which provides clinical services to people living with a range of neurological conditions including nervous system disorders such as motor neurone disease and chemotherapy-induced neuropathy. The team also work closely with ForeFront’s Frontier Clinic, a research clinic for people with frontotemporal dementia.

Working alongside the Motor Neurone Disease Group, Professor Steve Vucic leads the Neurodegenerative and Neuromuscular Diseases Research Group at the Westmead Institute. The team focuses on research to understand the underlying mechanisms behind neurodegenerative disorders such as motor neurone disease and frontotemporal dementia, as well as neuromuscular diseases like multiple sclerosis. A key issue for many patients is that treatment is delayed due to the lack of reliable diagnostic tests. Our focus is to develop novel diagnostic tests to improve the management of these conditions at the earliest timepoint for a better patient quality of life.

We are investigating a TMS technique shown to be sensitive in diagnosing motor neurone disease, which has potential application in multiple sclerosis and other degenerative disorders.

Investigating the primary pathogenesis, development, rate of progression and magnitude of nerve degeneration in a number of hereditary and acquired neurological diseases using nerve and cortical excitability studies.

Assessing the practical impact of motor neurone disease on patients and their family members

Additional projects

Investigating what influences patients’ decision-making for symptom management and quality of life.

Identifying the phenotype of the C9orf72 mutation in patients with motor neurone disease, frontotemporal dementia and FTD-MND.

Understanding the type of cellular changes that occur in the brain and spinal cord to determine treatable cellular causes.

Launched in 2005, this registry strives to improve patient care through continuous evaluation of patient management and outcomes. It also encourages scientific research collaborations to further our understanding of motor neurone disease. Visit the Australian Motor Neurone Disease Registry for more information.

Reducing the impact of these symptoms on the quality of life of patients and carers by examining their underlying causes using imaging methods and endocrine analysis.

Developing a biomarker platform to differentiate between clinical, pathological and genetic subtypes and to track changes in the levels of these proteins over time – this could enable early detection and characterisation of motor neurone disease and assist with monitoring future mechanistic therapies.

Correlating clinical phenotypes with immunological and neurophysiological profiles associated with inflammatory neuropathies to assist in promoting diagnostic accuracy, assessment of prognosis and predicting response to treatment. We also hope to identify biomarkers that can be used to monitor the response to treatment with IVIg (intravenous immunoglobulin).

Key publications

Early reports of cognitive and behavioural deficits in motor neuron disease might have been overlooked initially, but the concept of a frontotemporal dementia-motor neuron disease continuum has emerged during the past decade. Frontotemporal dementia-motor neuron disease is now recognised as an important dementia syndrome, which presents substantial challenges for diagnosis and management. Frontotemporal dementia, motor neuron disease, and frontotemporal dementia-motor neuron disease are characterised by overlapping patterns of TAR DNA binding protein (TDP-43) pathology, while the chromosome 9 open reading frame 72 (C9orf72) repeat expansion is common across the disease spectrum. Indeed, the C9orf72 repeat expansion provides important clues to disease pathogenesis and suggests potential therapeutic targets. Variable diagnostic criteria identify motor, cognitive, and behavioural deficits, but further refinement is needed to define the clinical syndromes encountered in frontotemporal dementia-motor neuron disease.

Learn more

Metabolic changes incorporating fluctuations in weight, insulin resistance, and cholesterol concentrations have been identified in several neurodegenerative disorders. Whether these changes result from the neurodegenerative process affecting brain regions necessary for metabolic regulation or whether they drive the degenerative process is unknown. Emerging evidence from epidemiological, clinical, pathological, and experimental studies emphasises a range of changes in eating behaviours and metabolism in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS, metabolic changes have been linked to disease progression and prognosis. Furthermore, changes in eating behaviour that affect metabolism have been incorporated into the diagnostic criteria for FTD, which has some clinical and pathological overlap with ALS. Whether the distinct and shared metabolic and eating changes represent a component of the proposed spectrum of the two diseases is an intriguing possibility. Moreover, future research should aim to unravel the complex connections between eating, metabolism, and neurodegeneration in ALS and FTD, and aim to understand the potential for targeting modifiable risk factors in disease development and progression.

Learn more

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular and pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of which TDP-43 is a major component, are a characteristic pathological feature of most ALS and FTD patients. Here we use genome-wide linkage analysis in a large ALS/FTD kindred to identify a novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified a CCNF missense mutation at this locus. Interrogation of international cohorts identified additional novel CCNF variants in familial and sporadic ALS and FTD. Enrichment of rare protein-altering CCNF variants was evident in a large sporadic ALS replication cohort. CCNF encodes cyclin F, a component of an E3 ubiquitin-protein ligase complex (SCF(Cyclin F)). Expression of mutant CCNF in neuronal cells caused abnormal ubiquitination and accumulation of ubiquitinated proteins, including TDP-43 and a SCF(Cyclin F) substrate. This implicates common mechanisms, linked to protein homeostasis, underlying neuronal degeneration.

Learn more

The aim of the study was to assess the utility of a novel amyotrophic lateral sclerosis (ALS) diagnostic index (ALSDI).

A prospective multicenter study was undertaken on patients presenting with suspected ALS. The reference standard (Awaji criteria) was applied to all patients at recruitment. Patients were randomly assigned to a training (75%) and a test (25%) cohort. The ALSDI was developed in the training cohort and its diagnostic utility was subsequently assessed in the test cohort.

The ALSDI reliably differentiates ALS from mimicking disorders at an early stage in the disease process.

Learn more