Towards a world free from Motor Neurone Disease (MND)

Our lab is interested in understanding how metabolic homeostasis at the systemic and cellular level can impact upon neurodegenerative processes.

Our Metabolic Exploration in Neurodegenerative Disease (MEND) research program centres on Motor Neurone Disease (MND), a fatal neurological condition in which the average life expectancy is 27 months following diagnosis. In MND, the irreversible degeneration of neurones in the central nervous system leads to progressive paralysis and eventually, death. There is no effective treatment for MND, and hence no cure.

We collaborate with clinicians and scientists across the world and Australia, and this underpins our strong translational, transdisciplinary, and multidisciplinary research foundation. Because MND is a complex, heterogeneous, and multifactorial condition, we are undertaking a range of projects that span the clinical and basic sciences with the ultimate goal of identifying viable strategies that can be rapidly implemented in the clinic to improve quality of life and prognosis for patients who are currently under our care, and for those who will be diagnosed with MND in the future.

Patient-directed research

We work very closely with people who are living with MND, their families, caregivers and friends. Our patient-directed research is based at our clinical sites and is primarily overseen by Dr Steyn. We are assessing body composition and metabolic rate, as well as dietary intake and appetite regulation, and gut dynamics to understand the impact of altered whole body metabolism and human physiology on the clinical features of disease and patient outcome.

Laboratory models of MND

We are using mouse models of MND, and human myosatellite cell-derived muscle fibres and human induced pluripotent stem cell (iPSC)-derived neurons to not only understand the mechanistic nature of MND, but to also conduct pre-clinical testing of potential therapeutic compounds. The combined use of mouse and human-derived models are integral to our goal of translating research findings into clinical trials for MND.

Our projects are based at The Royal Brisbane & Women’s Hospital, The Wesley Hospital, The University of Queensland, and multiple national and international sites (hyperlinked to lab members). Our projects are funded by the National Health and Medical Research Council, the Motor Neurone Disease Research Institute of Australia, the Royal Brisbane & Women’s Hospital Foundation, Wesley Medical Research, The MND and Me Foundation, and The University of Queensland.

Given that no two MND patients are the same, the projects within our MEND research program are focussed towards gaining insights that will form the basis upon which we can develop metabolically-directed therapeutic strategies that are personalised to match the precise metabolic needs of individual MND patients.

Our projects are built on a diverse, collaborative and strong translational, transdisciplinary, and multidisciplinary research foundation. MEND spans the disciplines of neurology, neuroscience, pharmacology, endocrinology and metabolism, physiology, healthy ageing, genetics, and stem cell biology. If you are an enthusiastic, passionate, driven, and talented individual who is interested in joining our research program, please contact Shyuan.

Metabolic dynamics in human MND

There is increasing evidence to suggest that metabolic imbalance contributes to earlier death in MND. We are currently conducting a multi-centre study that assesses the energy needs of people living with MND.

Projects in this arm of our research program investigate whether an imbalance between energy use at rest, the energy cost associated with eating, digesting and absorbing energy from food, and the energy used during physical activity in MND patients can affect the rate of disease progression. Knowledge gained from these studies will allow us to identify novel targets that we can modify to help the body to sustain optimal energy needs throughout the course of disease. In the long-term, this will help us to develop rational strategies to improve energy balance in MND, which will ultimately improve prognosis for MND patients.

Metabolism and skeletal muscle pathology in MND

Our studies into energy needs in MND show that people living with MND use more energy than expected (this is commonly called “hypermetabolism”). We have also generated data to show that hypermetabolism in MND patients may be associated with increased energy needs in skeletal muscle, which itself is already energy demanding.

Using mouse models of MND, and biopsies of skeletal muscle from MND patients and non-MND control subjects, we are conducting the first studies that correlate the energy needs in skeletal muscle with the systemic energy needs of MND mice and each individual human participant. The mechanistic insights gained from these projects will allow us to determine whether metabolically directed treatment strategies should target skeletal muscle to improve muscle pathology, metabolic balance and prognosis in MND.

Developing models to understand and treat MND using induced pluripotent stem cells (iPSCs)

Neurones are particularly active cells that continuously send signals around the body; this large workload places a considerable metabolic load on the neurones. If the energy demands of the neurones are not met, they will ultimately falter, and die.

In this project, we are developing iPSC-derived neurones from MND and non-MND subjects to assess neuronal bioenergetics. Insights gained from these iPSC-derived neurones will allow us to determine the impact of neuronal bioenergetics on disease pathogenesis. Using these iPSC-derived neurones, we aim to develop a high-throughput platform that will allow us to screen potential therapeutic candidates in MND, with the view to prevent neuronal death and thus, halt or slow disease progression in MND.

2016

Li, R., Steyn, F.J., Stout, M.B., Lee, K., Cully, T.R., Calderon, J.C., and Ngo, S.T. 2016.
Development of a high-throughput method for real-time assessment of cellular metabolism in intact long skeletal muscle fibre bundles.
The Journal of Physiology. doi: 10.1113/JP272988.
URL: Li et al, 2016

Ioannides, Z.A. Ngo, S.T., Henderson, R.D., McCombe, P.A., and Steyn, F.J. 2016.
Altered metabolic homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of energy imbalance and contribution to disease progression.
Neurodegenerative Diseases. 16 (5-6):382-397.
URL: Ioannides et al, 2016 

2015

Ngo, S.T., and Steyn, F.J. 2015.
The interplay between metabolic homeostasis and neurodegeneration: insights into the neurometabolic nature of Amyotrophic Lateral Sclerosis.
Cell Regen (Lond). 4 (1): 5.
URL: Ngo and Steyn 2015 

Ngo, S.T., Steyn, F.J., Huang, L., Mantovani, S., Pfluger, C., Woodruff, T.M., O'Sullivan, J.D., Henderson, R.D., and McCombe, P.A. 2015.
Altered expression of metabolic proteins and adipokines in patients with amyotrophic lateral sclerosis (ALS).
Journal of the Neurological Sciences. 357 (1-2): 22-27.
URL: Ngo et al, 2015 

Palamiuc, L., Schlagowski, A., Ngo, S.T., Vernay, A., Grosch, S., Henriques, A., Boutillier, A-L., Zoll, J., Echaniz-Laguna, A., Loeffler, J-P., and René, F. 2015.
A metabolic switch towards lipid use in glycolytic muscle is an early pathologic event in a mouse model of Amyotrophic Lateral Sclerosis.
EMBO Molecular Medicine. 7: 524-46.
URL: Palamuic et al, 2015 

2014

Ngo, S.T., Steyn, F.J., and McCombe, P.A. 2014.
Gender differences in autoimmune disease.
Frontiers in Neuroendocrinology. 35 (3): 347-369.
URL: Ngo et al, 2014 

Ngo, S.T. Steyn, F.J., and McCombe, P.A. 2014.
Body mass index and dietary intervention: implications for prognosis of Amyotrophic Lateral Sclerosis.
Journal of the Neurological Sciences. 340 (1-2): 5-12.
URL: Ngo et al, 2014 

2013

Steyn, F.J., Lee, K., Fogarty, M.J., Veldhuis, J.D., McCombe, P.A., Bellingham, M.C., Ngo, S.T., and Chen, C. 2013.
Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male Amyotrophic Lateral Sclerosis mice.
Endocrinology. 154 (12): 4695-4706.
URL: Steyn et al, 2013 

2012

Steyn, F.J., Ngo, S.T., Lee, J.D., Leong, J.W., Buckley, A.J., Veldhuis, J.D., McCombe, P.A., Chen, C., and Bellingham, M.C. 2012.
Impairments to the GH-IGF1 axis in hSOD1G93A mice give insight into possible mechanisms of GH dysregulation in patients with Amyotrophic Lateral Sclerosis.
Endocrinology. 153 (8): 3735-3746.
URL: Steyn et al, 2012 

Ngo, S.T., Baumann, F., Ridall, P.G., Pettitt, A.N., Henderson, R.D., Bellingham, M.C., and McCombe, P.A. 2012.
The relationship between Bayesian motor unit number estimation and histological measurements of motor neurons in wild-type and SOD1G93A mice.
Clinical Neurophysiology. 123 (10): 2080-91.

URL: Ngo et al, 2012 

Lab head

  • Dr Shyuan Ngo

    Scott Sullivan Research Fellow MND
    Biomedical Sciences

Staff

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As scientists, we are obligated to share our research discoveries and to contribute to the communities we serve. Those who form part of our MEND research program are actively involved in events that are aimed at raising funding and awareness for MND. We work closely with the MND and Me Foundation and with the State MND Associations that form part of MND Australia. We are passionate about our community, and we are proud and humbled to serve the wider MND community.

Ceal Research

Thanks to the generous support of our donors, we continue to conduct research that works towards a world free of MND.

To donate to our Metabolic Exploration in Neurodegenerative Disease (MEND) research program into MND (MEND-MND), that sees our clinical core based at the multidisciplinary MND clinic at the Royal Brisbane & Women’s Hospital, please click the Donate button below. Once at the donation site, you can use the “Select Campaign” drop down menu to choose "Metabolic Exploration in Neurodegenerative Disease (MEND)” to ensure that your donation is used to support our research.

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Find out more about our research environment and how to apply to do a short or long-term research project with us.