Protecting Nerve Cells from MS Injury

Project Outcomes

Current treatments reduce attacks of MS symptoms by 30 - 70% and unfortunately do not prevent the progressive increase in disability, says Professor Helmut Butzkueven.

Professor Butzkueven’s research used an animal model to identify the natural repair processes and assess if treatments designed to enhance naturally occurring repair may provide additional benefits.

Of particular interest are the axons, the cables transmitting electricity between cells of the nervous system which do not regenerate when cut by autoimmune damage. In a specific animal model of MS, Professor Butzkueven has been able to map and measure axonal damage.  This means that researchers can now measure the effect new treatments have on protecting and preventing axons.

The investigation of a potential neuroprotective treatment has shown to be clinically beneficial reducing axon damage. Professor Butzkueven will continue to develop this into a treatment for human clinical trials.

Publications

• Validation of linear cerebral atrophy markers in multiple sclerosis. Butzkueven H, Kolbe SC (Joint first authors), Jolley DJ, Brown JY, Cook MJ, van der Mei IAF, Groom PS, Carey J, Eckholdt J, Rubio JP, Taylor BV, Mitchell PJ, Egan GF, Kilpatrick TJ  J Clin Neurosci  2008 15:130-137
• MR diffusion changes correlate with ultra-structurally defined axonal degeneration in murine optic nerve.  H Butzkueven, Q Wu (Joint first authors), M Gresle, F Kirchhoff, A Friedhuber, QYang, H Wang, K Fang, H Lei, G Egan, TJ Kilpatrick. Neuroimage 2007 37:1138-1147 (2006 IF 5.56)
• Leukemia Inhibitory Factor signalling modulates both central nervous system demyelination and myelin repair. Marriott MP, Emery B, Cate HS, Binder MD, Kemper D, Wu Q, Kolbe S, Gordon IR, Wang H, Egan G, Murray S, Butzkueven H, Kilpatrick TJ Glia 2008; 56:686-698
• Gas6 deficiency increases oligodendrocyte loss and microglial activation in response  to cuprizone-induced demyelination.  Binder M, Cate HS,  Prieto AL, Kemper D,   Butzkueven H, Gresle MM, Cipriani T, JokubaitisVJ, Carmeliet P, Kilpatrick TJ.  J   Neurosci 2008; 28:5195-5206
• Validation of a novel biomarker for acute axonal injury in experimental autoimmune encephalomyelitis Gresle, M.M., Shaw, G., Jarrott, B., Alexandrou, E.N., Friedhuber, A.M., Kilpatrick, T.J., Butzkueven, H.  J Neurosci Res2008;86:3548-3555.
• Optic nerve diffusion changes and atrophy jointly predict visual dysfunction after optic neuritis. Kolbe S, Chapman C, Nguyen T, Bajraszewski C, Johnston L, Kean M, Mitchell PJ, Butzkueven H, Paine M, Kilpatrick TJ, Egan G.NeuroImage 2009;45:679-686.
• Measurement of disability in Multiple Sclerosis. Gray O and Butzkueven H. Neurology Asia 2008;13:153-159
• How to diagnose multiple sclerosis and what are the pitfalls. Shaw C, Chapman C and Butzkueven H. Internal Medicine Journal 2009; 39:792-799.
• A role for galanin in human and experimental inflammatory demyelination. Wraith DC, Pope R, Butzkueven H, Holder H, Vanderplank P, Lowrey P, Day MJ, Gundlach A, Kilpatrick TJ, Scolding N, Wynick D, PNAS 2009 106:15466-15471
• Neuroprotection in Multiple Sclerosis: a therapeutic challenge for the next decade. Van der Walt A, Butzkueven H, Kolbe S, Marriott M, Alexandrou E, Gresle M, Egan G, Kilpatrick T.  Pharmacology and Therapeutics 2010 126, 82-93
• Neurofilament Proteins as Body Fluid Biomarkers of Neurodegeneration in Multiple Sclerosis. Gresle M, Butzkueven H, and Shaw G. Multiple Sclerosis International, 2011, doi:10.1155/2011/315406
• Diffusion Tensor Imaging of the Optic Radiations after Optic Neuritis. Kolbe S, Bajraszewski C, Chapman C, Nguyen,T, Mitchell P, Paine M, Butzkueven H, Johnston L, Kilpatrick TJ, and Egan G. Human Brain Mapping, 2011, Sep 13. doi:10.1002/hbm.21343.
• Vaginally administered PEGylated LIF antagonist blocked embryo implantation and eliminated non-target effects on bone in mice. Menkhorst E, Zhang JG, Sims NA, Morgan PO, Soo P, Poulton I, Metcalf D, Alexandrou S, Gresle M, Salamonsen LA, Butzkueven H, Nicola NA, Dimitriadis E. PLoS One, 2011;6(5):e19665.
• Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels. Duce JA, Ayton S, Miller AA, Tsatsanis A, Lam LQ, Leone L, Corbin JE, Butzkueven H, Kilpatrick TJ, Rogers JT, Barnham KJ, Finkelstein DI, Bush AI. Mol Psychiatry. 2013;18:245-254
• Diffusion tensor imaging correlates of visual impairment in multiple sclerosis and chronic optic neuritis. Kolbe SC, Marriott M, van der Walt A, Fielding J, Klistorner A, Mitchell PJ, Butzkueven H, Kilpatrick TJ, Egan GF. Invest Ophthalmol Vis Sci. 2012;53:825-832.
• Diffusion tensor imaging of acute inflammatory lesion evolution in multiple sclerosis Y Liu, PJ Mitchell, TJ Kilpatrick, MS Stein, LC Harrison, J Baker, M Ditchfield, K Li ,GF Egan, H. Butzkueven (equal last author), SC Kolbe (equal last author); J Clin Neurosci. 2012;19:1689-1694.
• Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism Gresle, MM, Alexandrou, EN, Wang, B, Wu Q, Egan, G, Ayres, M, Jonas, A.K, Doherty, W, Friedhuber, AM, Shaw, G, Sendtner, M, Kilpatrick, T.J, Butzkueven, H. PLoS One. 2012;7:e47379.
• EphA4 receptor tyrosine kinase is a modulator of onset and disease severity of Experimental Autoimmune Encephalomyelitis (EAE) Munro, K.M, Dixon, K.J., Gresle, M. , Jonas, A. Kemper, D, Doherty, W, Pearse, M, Boyd, A.W, Kilpatrick, Butzkueven, H., Turnley, A.M. (equal last author), PLoS One. 2013;8(2):e55948