Animal models of multiple sclerosis

The study of MS requires a reductionist approach whereby the disease is best studied using animal models. To that effect, we are using experimental autoimmune encephalomyelitis (EAE), an acute central nervous system inflammatory model, induced with highly immunogenic components (or their peptides) of the brain. Notably, we have generated relapsing-remitting (RR) and chronic progressive (CP) models that mimic many features seen in the human disease, including genetic, immunological and pathological aspects. This allows us to not only study the mechanisms involved in the pathogenesis of MS but also to develop and test novel therapeutic approaches for this severe debilitating neurodegenerative disorder. To better understand the mechanism of CNS repair without the complication of the inflammatory pathology, we are using a model of chemically induced-demyelination, the “cuprizone model”.

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Kinzel S, Lehmann-Horn K, Torke S, Häusler D, Winkler A, Stadelmann C, Payne N, Feldmann L, Saiz A, Reindl M, Lalive PH, Bernard CC, Brück W, Weber MS.

Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen.

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CNS accumulation of regulatory B cells is VLA-4-dependent.

Neurol Neuroimmunol Neuroinflamm. 2016 Mar 9;3(2):e212. doi: 10.1212/NXI.0000000000000212. eCollection 2016 Apr.

Klaus Lehmann-Horn, S.A.S., Claude C.A. Bernard, Raymond A. Sobel ,Scott S. Zamvil.,

B cell VLA-4-deficiency reduces leukocyte recruitment and susceptibility to autoimmune encephalomyelitis.

Ann Neurol. 2015 May;77(5):902-8. doi: 10.1002/ana.24387. Epub 2015 Mar 28.

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APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation.

Cell Death Dis. 2015 Feb 19;6:e1651. doi: 10.1038/cddis.2015.10.

Xiangting Chen, J.M.K., John V Forrester, Gabrielle L Goldberg, Ian P Wicks, Claude C Bernard and Paul G McMenamin.

In vivo multi-modal imaging of experimental autoimmune uveoretinitis in transgenic reporter mice reveals dynamic nature of inflammatory changes during disease progression.

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Payne, N.L., A. Sylvain, C. O'Brien, D. Herszfeld, G. Sun, and C.C. Bernard

Application of human induced pluripotent stem cells for modeling and treating neurodegenerative diseases.

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Single beta(3)-amino acid substitutions to MOG peptides suppress the development of experimental autoimmune encephalomyelitis.

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Robinson, A.M., S. Sakkal, A. Park, V. Jovanovska, N. Payne, S.E. Carbone, S. Miller, J.C. Bornstein, C. Bernard, R. Boyd, and K. Nurgali

Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis.

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Herszfeld, D., N.L. Payne, A. Sylvain, G. Sun, C.C. Bernard, J. Clark,H. Sathananthan

Fine Structure of Neurally Differentiated iPS Cells Generated from a Multiple Sclerosis (MS) Patient: A Case Study.

Microsc Microanal. 2014 Dec;20(6):1869-75. doi: 10.1017/S1431927614013312. Epub 2014 Oct 22.

Herszfeld, D., N.L. Payne, A. Sylvain, G. Sun, C.C. Bernard, J. Clark, and H. Sathananthan

Fine structure of neurally differentiated iPS cells generated from a multiple sclerosis (MS) patient: a case study.

Microsc Microanal. 2014 Dec;20(6):1869-75. doi: 10.1017/S1431927614013312. Epub 2014 Oct 22.

Tafreshi, A.P., N. Payne, G. Sun, A. Sylvain, K. Schulze, and C. Bernard

Inactive GSK3beta is disturbed in the spinal cord during experimental autoimmune encephalomyelitis, but rescued by stem cell therapy.

Neuroscience. 2014 Sep 26;277:498-505. doi: 10.1016/j.neuroscience.2014.07.013. Epub 2014 Jul 23.

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Neurol Neuroimmunol Neuroinflamm. 2014 Aug 14;1(2):e22. doi: 10.1212/NXI.0000000000000022. eCollection 2014.

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Quantitative proteome profiling of CNS-infiltrating autoreactive CD4+ cells reveals selective changes during experimental autoimmune encephalomyelitis.

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McDonald, C.A., Short, Martin, Jenkin, Graham and Bernard, Claude Charles Andre

The Potential of Human Amnion Epithelial Cells as an Immunomodulatory and Neuroregenerative Treatment for Multiple Sclerosis

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Lehmann-Horn, K., S. Kinzel, L. Feldmann, F. Radelfahr, B. Hemmer, S. Traffehn, C.C. Bernard, C. Stadelmann, W. Bruck, and M.S. Weber

Intrathecal anti-CD20 efficiently depletes meningeal B cells in CNS autoimmunity.

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Chung, J.Y., W. Figgett, K. Fairfax, C. Bernard, J. Chan, B.H. Toh, F. Mackay, and F. Alderuccio

Gene therapy delivery of myelin oligodendrocyte glycoprotein (MOG) via hematopoietic stem cell transfer induces MOG-specific B cell deletion.

J Immunol. 2014 Mar 15;192(6):2593-601. doi: 10.4049/jimmunol.1203563. Epub 2014 Feb 14.

Wang, C.K., C.W. Gruber, M. Cemazar, C. Siatskas, P. Tagore, N. Payne, G. Sun, S. Wang, C.C. Bernard, and D.J. Craik

Molecular grafting onto a stable framework yields novel cyclic peptides for the treatment of multiple sclerosis.

ACS Chem Biol, 2014. 9(1): p. 156-63. doi: 10.1021/cb400548s.

Zhou, K., G. Thouas, C. Bernard, and J.S. Forsythe

3D presentation of a neurotrophic factor for the regulation of neural progenitor cells.

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Varrin-Doyer, M., A. Shetty, C.M. Spencer, U. Schulze-Topphoff, M.S. Weber, C.C. Bernard, T. Forsthuber, B.A. Cree, A.J. Slavin, and S.S. Zamvil

MOG transmembrane and cytoplasmic domains contain highly stimulatory T-cell epitopes in MS.

Neurol Neuroimmunol Neuroinflamm, 2014. 1(2): p. e20. doi: 10.1212/NXI.0000000000000020.

Payne, N.L., G. Sun, C. McDonald, L. Moussa, A. Emerson-Webber, S. Loisel-Meyer, J.A. Medin, C. Siatskas, and C.C. Bernard

Human adipose-derived mesenchymal stem cells engineered to secrete IL-10 inhibit APC function and limit CNS autoimmunity.

Brain Behav Immun. 2013 May;30:103-14. doi: 10.1016/j.bbi.2013.01.079. Epub 2013 Jan 29.

Payne, N.L., G. Sun, C. McDonald, D. Layton, L. Moussa, A. Emerson-Webber, N. Veron, C. Siatskas, D. Herszfeld, J. Price, and C.C. Bernard

Distinct immunomodulatory and migratory mechanisms underpin the therapeutic potential of human mesenchymal stem cells in autoimmune demyelination.

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Litwak, S.A., N.L. Payne, N. Campanale, E. Ozturk, J.Y. Lee, S. Petratos, C. Siatskas, M. Bakhuraysah, and C.C. Bernard

Nogo-receptor 1 deficiency has no influence on immune cell repertoire or function during experimental autoimmune encephalomyelitis.

PLoS One. 2013 Dec 5;8(12):e82101. doi: 10.1371/journal.pone.0082101. eCollection 2013.

Hou, Z.L., Y. Liu, X.H. Mao, C.Y. Wei, M.Y. Meng, Y.H. Liu, Z. Zhuyun Yang, H. Zhu, M. Short, C. Bernard, and Z.C. Xiao

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Cell Adh Migr. 2013 Sep-Oct;7(5):404-7. doi: 10.4161/cam.26941. Epub 2013 Oct 30.

Chen, X., J. Kezic, C. Bernard, and P.G. McMenamin

Rd8 mutation in the Crb1 gene of CD11c-eYFP transgenic reporter mice results in abnormal numbers of CD11c-positive cells in the retina.

J Neuropathol Exp Neurol. 2013 Aug;72(8):782-90. doi: 10.1097/NEN.0b013e31829e8375.