Motor Neurone Disease Group
Neurodegenerative diseases have a devastating impact on quality of life and impose a tremendous burden on the health care system. Motor neurone disease (MND) is the most rapidly fatal, with increasing physical disability and death typically within 2-3 years from symptom onset.
Our group has a broad interest in developing and delivering new therapeutics for MND using pioneering stem cell and animal models.
About our research
Our group is primarily focused on understanding the molecular basis of motor neurone disease (MND), also called amyotrophic lateral sclerosis (ALS), to inform rational drug development for treatment. We also research other neurodegenerative diseases affecting motor neurons, including spinal muscular atrophy (SMA) and spinal bulbar muscular atrophy (SBMA), more commonly known as Kennedy’s disease (KD).
Key research questions
- What is the fundamental cause of ALS?
- When does motor neuron vulnerability start in ALS?
- Where does ALS originate in the central nervous system?
- What is the primary cell death pathway(s) mediating motor neuron loss in ALS?
- How early do we need to intervene with treatments in ALS?
- Do ALS, SMA and KD share a common pathogenesis?
- Motor neurone disease (MND)
- Amyotrophic lateral sclerosis (ALS)
- Primary lateral sclerosis (PLS)
- Spinal muscular atrophy (SMA)
- Kennedy’s disease (KD)
- Frontotemporal dementia (FTD)
Our team employs a combination of cell and molecular biology to unravel MND pathogenesis in patient-derived biosamples, cell culture systems and animal models. We seek to identify and understand the primary mechanisms underlying motor neuron vulnerability and degeneration in MND, while translating our discoveries into relevant targets for effective intervention. Our group is particularly known for pioneering new and improved models of MND using induced pluripotent stem cell (iPSC) technology, organoids, chemogenetics and genome editing.
Our major outcomes
- Establishing a large-scale, population-wide library of induced pluripotent stem cells (iPSCs) from Australian MND patients pre-validated for disease phenotypes and drug efficacy (ID MND Initiative).
- Establishing a multi-omic dataset from Australian MND patient iPSC-derived motor neurons combining deep longitudinal clinical, genomic, transcriptomic and metabolomic profiles to understand heterogeneity (Precision Medicine Program).
- Our preclinical findings have directly contributed to 5 clinical trials for MND, including re-purposing of the generic drug ambroxol for ALS which is currently under Phase 2 clinical trial.
- Stem cell technology
- Advanced imaging techniques and 3D image analysis
- Multi-omics, including transcriptomics and metabolomics
- Antisense oligonucleotides
- High throughput drug screening
- Animal behaviour
- Molecular biology
- Genetic engineering
- Genome editing
- CRISPR screens
‘Our research is empowered by the MND Community. From people with MND who generously donate precious cells to our drug screening program to the army of donors and patient-founded organisations who tirelessly support our research for a cure.’
- Defining unique molecular markers of upper motor neurons in MND
- Developing SMN gene therapy for SMA and MND
- Investigating age-related effects of autophagy on neuroglial cells
- Investigating autophagy pathway dynamics at the neuromuscular junction
- Making spinal cord organoids from patient-derived induced pluripotent stem cells
- Jibao (Jack) Yuan
- Lijun Loh
- Roaul Das
- Matteo Pitteri
- Katherine Lewis
- Chau Tran
- Aida Viden
- Francois-Xavier Beau
- Naween Fernando
- Wang, T., Tomas, D., Perera, N.D., Cuic, B., Luikinga, S., Viden, A., Barton, S.K., McLean, C.A., Samson, A.L., Southon, A., Bush, A.I., Murphy, J.M. and Turner, B.J. (2021). Ferroptosis mediates selective motor neuron death in amyotrophic lateral sclerosis. Cell Death & Differentiation, [online] pp.1–12. doi:https://doi.org/10.1038/s41418-021-00910-z.
- Perera, N.D., Tomas, D., Wanniarachchillage, N., Cuic, B., Luikinga, S.J., Rytova, V. and Turner, B.J. (2021). Stimulation of mTOR-independent autophagy and mitophagy by rilmenidine exacerbates the phenotype of transgenic TDP-43 mice. Neurobiology of Disease, 154, p.105359. doi:https://doi.org/10.1016/j.nbd.2021.105359.
- Wang, T., Perera, N.D., Chiam, M.D.F., Cuic, B., Wanniarachchillage, N., Tomas, D., Samson, A.L., Cawthorne, W., Valor, E.N., Murphy, J.M. and Turner, B.J. (2019). Necroptosis is dispensable for motor neuron degeneration in a mouse model of ALS. Cell Death & Differentiation, 27(5), pp.1728–1739. doi:https://doi.org/10.1038/s41418-019-0457-8.
- Sheean, R.K., McKay, F.C., Cretney, E., Bye, C.R., Perera, N.D., Tomas, D., Weston, R.A., Scheller, K.J., Djouma, E., Menon, P., Schibeci, S.D., Marmash, N., Yerbury, J.J., Nutt, S.L., Booth, D.R., Stewart, G.J., Kiernan, M.C., Vucic, S. and Turner, B.J. (2018). Association of Regulatory T-Cell Expansion With Progression of Amyotrophic Lateral Sclerosis. JAMA Neurology, 75(6), p.681. doi:https://doi.org/10.1001/jamaneurol.2018.0035.
- Perera, N.D., Sheean, R.K., Lau, C.L., Shin, Y.S., Beart, P.M., Horne, M.K. and Turner, B.J. (2018). Rilmenidine promotes MTOR-independent autophagy in the mutant SOD1 mouse model of amyotrophic lateral sclerosis without slowing disease progression. Autophagy, [online] 14(3), pp.534–551. doi:https://doi.org/10.1080/15548627.2017.1385674.