Multiple sclerosis (MS) is the most common neurodegenerative disease that affects young adults in our community and is widely considered to be an enigmatic disease that involves autoimmune mechanisms, but whose severity is dependent upon the nature of the neurobiological response to injury. Our MS Division strives to understand the cause of the disease and to develop better therapies to treat the condition. To achieve these aims, we are focusing on several areas, including the genetic determinants of MS, the potential of neuroprotective and regenerative medicine and the development of novel prognostic indicators.

Our genetics research has identified two novel loci that confer susceptibility to multiple sclerosis. One of these loci appears to influence the expression of the CD40 protein, which modulates key aspects of immune function and which has also been implicated in the pathogenesis of other autoimmune diseases, notably Grave’s disease and rheumatoid arthritis. The other locus encodes a region of the genome that encompasses some 17 genes, including key candidate genes involved in Vitamin D metabolism, which we and others have previously shown to be potentially important in the susceptibility to MS.

Our focus on regenerative medicine follows on from seminal work performed some years ago which we contributed to, that identified stem cell populations within discrete regions of the adult mammalian brain, in particular the subventricular zone (SVZ). By studying the molecular response of the SVZ to a demyelinative insult, we have identified candidate genes that are potentially important in modulating regeneration. One important set of candidates is the bone morphogenic protein family and we are currently exploring the influence of this series of factors on precursor cells and their progeny during demyelination.

Another area of interest is to develop strategies focusing on cellular protection, designed to potentiate the survival of either the oligodendrocyte, the myelinating cell of the central nervous system or neurons. We have a strong tradition in this area, having previously identified that molecular signaling induced by the growth factor, LIF, is a key component of the protective response initiated within oligodendrocytes, as a consequence of a demyelinative insult in vivo. Our more recent work has identified that the TAM family of receptor tyrosine kinases and their ligand Gas6 are also important in promoting oligodendrocyte survival but also in modulating innate immune activity during central demyelination.

We are also developing biomarkers of disease severity and continue to be encouraged by work that has shown that release into the serum of the neurofilament heavy chain from damaged neurons could be a reliable and valid marker of ongoing neuronal damage. Such a marker should prove invaluable in future clinical studies designed to assess the efficacy of novel neuroprotective and regenerative therapies in MS.

Collaborative Links


Dr James Bourne
Australian Regenerative Medicine Institute, Monash University
Neural precursor cell biology in the non-human primate

Associate Professor Anne Turnley
Centre for Neuroscience, University of Melbourne
Stefania Castelletto
Melbourne Materials Institute, University of Melbourne
Application of nanoparticle technology to the study of neural stem cell responses in vivo

Catriona McLean, Director
Department of Anatomical Pathology, The Royal Prince Alfred Hospital, Victoria, Australia
The role of Gas6 and the TAM receptors in central demyelination

Dr Rachel Hill and Professor Maarten van den Buuse
Behavioural Neuroscience Laboratory, Mental Health Research Institute, Victoria
Brain-derived neurotrophic factor expression is increased in the hippocampus of 5-HT(2C) receptor knockout mice

Professor Gary Egan
The Florey Institute of Neuroscience and Mental Health
Neuroimaging in MS and in mouse models of demyelination

Associate Professor Andrew Gundlach
The Florey Institute of Neuroscience and Mental Health
Role of Galanin in demyelination

Dr Tony Hughes
Dept. Parmacology, University of Melbourne
Neurotrophin mimetics

Associate Professor Graham Barrett
Dept. Physiology, University of Melbourne
Role of the low affinity neurotrophin receptor in myelination

Professor Perry Bartlett and Professor Pankaj Sah
Queensland Brain Institute
Investigation of the functional role of neural precursor cells in hippocampal learning and memory

Professor Simon Foote
Menzies Research Institute
Genetics of Multiple Sclerosis

Professor Tony McMichael
Australian national University, Canberra
Associate Professor Anne-Louise Ponsonby
Murdoch Children’s Research institute
Role of environmental factors in MS: Ausimmune study


Professor Greg Lemke
The Salk Institute for Biological Studies, La Jolla, USA
The role of Gas6 and the TAM receptors in central demyelination

Professor Samuel David
McGill University, Canada
Iron metabolism in MS

Professor David Wynick
Bristol University, UK
Role of Galanin in demyelination

Associate Professor Bruce Carter
Vanderbilt University, USA
Neurotrophin signaling in myelinating cells

Professor Luis Parada
University of Texas Southwestern, USA
Role of TrkB in central demyelination

Professor Gerry Shaw
McKnight Brain Institute of the University of Florida
Biomarkers of neuronal damage and disease severity

Associate Professor Tanja Kuhlmann
Institute of Neuropathology, University Hospital Münster, Münster, Germany
Role of Dab2 in central demyelination