Multiple Sclerosis Group

Group Leader
Professor Trevor Kilpatrick, MBBS, PhD, FRACP

Research Fellows
Dr Helmut Butzkueven, MB BS Melb FRACP PhD(Melb)
Dr Holly Cate, BSc [Univ Nth Carolina], MSc [Univ Nth Carolina], PhD [Georgia State Univ]
Dr Simon Murray, BSc (Hons) [Uni Melb], BAppSci (Physiotherapy) [LaTrobe], PhD [Mon]
Dr Junhua Xiao, MB BS (Nanjing Med. Uni), PhD(Melb)

Research Assistants
Ms Michelle Binder, BSc (Hons) [Univ Syd], MSc [Univ Melb]
Ms Catherine Chang
Mr Tobias Merson, BA, BSc (Hons)
Ms Melissa Quick
Ms Pik Ying Soo, BSc [Monash]
Ms Agnes Wong, BBiomedSci (Univ Melb) BSc (Hons)

Graduate Students
Ms Vilija Jokubaitis, BCom/BSc (Hons) [Univ Melb] (PhD student)
Dr Mark Marriott, MBBS(Hons) [Monash], FRACP (PhD student)

The Multiple Sclerosis Group is focused on developing strategies to limit the severity of demyelinating diseases of the central nervous system, of which MS is the most common cause. Multiple sclerosis is thought to result from an autoimmune attack against myelin, which is produced by specialised glial cells known as oligodendrocytes that ensheath neurons. Whilst currently available therapies have some capacity to reduce disease activity via immunomodulatory mechanisms there are, as yet, no established treatments that either reduce oligodendrocytic damage or enhance nervous system repair, strategies that our laboratory is focusing upon.

In order to achieve these goals, we recognise the need to utilise state of the art technologies in molecular and cellular neurobiology, as well as to study whole animal models of demyelinating disease. We utilise genetically modified animals that express marker genes expressed by oligodendrocyte specific promoters in order to quantify oligodendrocytic rescue. We also generate conditional knockout mice in which key genes are selectively deleted from oligodendrocytes, in order to interrogate their influence upon these cells, both in health and in disease. Access to these technologies places us at the vanguard of basic laboratory research into demyelinating diseases.

Our previous work has established that the cytokine, leukemia inhibitory factor (LIF), enhances the viability of oligodendrocytes after a demyelinating insult and indicates that LIF receptor signaling is an important component of the endogenous oligodendroglial response to environmental stressors. Recent work has concentrated upon the actions of modulators of the LIF response, in particular the suppressors of cytokine signaling (SOCS). In particular, we have established that SOCS3 is a negative regulator of LIF signaling in oligodendrocytes, suggesting that the inhibition of SOCS activity within these cells might enhance the therapeutic utility of LIF. We are also investigating how other signaling molecules might either enhance oligodendrocytic viability or potentiate the capacity of precursor cells to differentiate into oligodendrocytes.

Publications

Grigg A, Tubridy NJ, Szer J, Mitchell P, Butzkueven H, Shuttleworth P, KILPATRICK TJ. Cladribine followed by autologous stem cell transplantation in progressive multiple sclerosis Internal Medical Journal 2004;34:66-9.

Coulson EJ, Reid K, Shipham K, Morley S, Kilpatrick TJ, Bartlett PF. The role of neurotransmission and the chopper domain in p75 NTR death signaling Progress in Brain Research 2004;146:41-62.

Taylor I, Butzkueven H, Litewka L, Cook M, Mitchell P, Kilpatrick TJ, Tubridy N. Serial MRI in multiple sclerosis: A prospective pilot study of lesion load, whole brain volume and thalamic atrophy J. Clin. Neurosci 2004;11:153-8.

Rubio JP, Bahlo M, Tubridy N, Wilkinson C, Johnson L, Butzkueven H, Marriott M, Carey J, Mraz G, Tait B, Speed TP, Foote SJ, Kilpatrick TJ. A common ancestral susceptibility haplotype in the HLA complex for multiple sclerosis and hemochromatosis. Hum Genet. 2004 May;114(6):573-80.

Petratos S , Gonzales MF, Azari MF, Marriott M, Minichiello RA, Shipham KA, Profyris C, Nicolaou A, Boyle A, Cheema SS, Kilpatrick TJ. Expression of the low affinity neurotrophin receptor p75NTR on oligodendrocyte progenitors in chronic active MS lesions Glia. 2004 Oct;48(1):64-75.

Turner BJ, Murray SS, Piccenna LG, Lopes EC, Kilpatrick TJ, Cheema SS. Effect of p75 neurotrophin receptor antagonist on disease progression in transgenic amyotrophic lateral sclerosis mice. J Neurosci Res. 2004 Oct 15;78(2):193

Kilpatrick TJ, Butzkueven H, Emery B, Marriott M, Taylor BV, Tubridy N. Neuroglial responses to CNS injury: prospects for novel therapeutics. Expert Rev Neurother. 2004 Sep;4(5):869-78.

Pitman M, Emery B, Binder M, Wang S, Butzkueven H, Kilpatrick, TJ. LIF Receptor Signalling Modulates Neural Stem Cell Renewal. Mol Cell Neurosci. 2004 Nov;27(3):255-66.

Ponsonby AL, van der Mei I, Dwyer T , Blizzard L, Taylor B , Kemp A, Simmons R, Kilpatrick TJ. Exposure to infant siblings during early life and risk of multiple sclerosis. JAMA 2005 Jan 26;293(4):463-9

Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, Marta M, Leite I, Dubois B, Rubio J, Butzkueven H, Kilpatrick T, Mycko MP, Selmaj KW, Rio ME, Sa M, Salemi G, Savettieri G, Hillert J, Compston DA. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005 Apr 12;64(7):1144-51

Laboratory Photos

Simon Murray