Neuroprotective dimethyl fumarate synergizes with immunomodulatory interferon beta to provide enhanced axon protection in autoimmune neuroinflammation

Experimental Neurology

Volumn 257, Issue , 2014, Pages 50-56

  Reick, Christiane ^a,b   Ellrichmann, Gisa ^a   Thöne, Jan ^a   Scannevin, Robert H ^c   Saft, Carsten ^a   Linker, Ralf A ^d   Gold, Ralf ^a,b  

^a ST JOSEF HOSPITAL   (Germany)

^b RUHR UNIVERSITY BOCHUM   (Germany)

^c BiogenIdec Inc   (United States)

^d UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Combination therapy; Dimethyl fumarate; EAE; Immunomodulation; Interferon beta; Multiple sclerosis; Neuroprotection

Indexed keywords

BETA INTERFERON; FUMARIC ACID DIMETHYL ESTER; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 6;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY SPECIFICITY; ANTIGEN PRESENTING CELL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CELL DIFFERENTIATION; CONFOCAL LASER MICROSCOPY; CONTROLLED STUDY; CYTOKINE PRODUCTION; DEMYELINATION; DISEASE SEVERITY; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; ENZYME SPECIFICITY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FEMALE; FLUORESCENCE MICROSCOPY; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; IMMUNOPHENOTYPING; MOUSE; NERVE FIBER; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SPLEEN CELL; T LYMPHOCYTE ACTIVATION;

COMBINATION THERAPY; DIMETHYL FUMARATE; EAE; IMMUNOMODULATION; INTERFERON-BETA; MULTIPLE SCLEROSIS; NEUROPROTECTION;

2',3'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; ANIMALS; ANTIGENS, CD3; ANTIGENS, DIFFERENTIATION; AXONS; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DRUG SYNERGISM; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FUMARATES; IMMUNOLOGIC FACTORS; INTERFERON-BETA; LYMPHOCYTES; MICE; MICE, INBRED C57BL; MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; NEUROFILAMENT PROTEINS; PEPTIDE FRAGMENTS; TIME FACTORS;

EID: 84899877751     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2014.04.003     Document Type: Article

References (40)

1. Barnabe-Heider F., Miller F.D. Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J. Neurosci. 2003, 23(12):5149-5160.
2. Bauer J., Sminia T., Wouterlood F.G., Dijkstra C.D. Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis. J. Neurosci. Res. 1994, 38(4):365-375.
3. Bauer J., Ruuls S.R., Huitinga I., Dijkstra C.D. The role of macrophage subpopulations in autoimmune disease of the central nervous system. Histochem. J. 1996, 28(2):83-97.
4. Brod S.A., Lindsey J.W., Wolinsky J.S. Combination therapy with glatiramer acetate (copolymer-1) and a type I interferon (IFN-alpha) does not improve experimental autoimmune encephalomyelitis. Ann. Neurol. 2000, 47(1):127-131.
5. Burks J. Interferon-beta1b for multiple sclerosis. Expert. Rev. Neurother. 2005, 5(2):153-164.
6. Calabresi P.A., et al. An open-label trial of combination therapy with interferon beta-1a and oral methotrexate in MS. Neurology 2002, 58(2):314-317.
7. Ellrichmann G., et al. Efficacy of fumaric acid esters in the R6/2 and YAC128 models of Huntington's disease. PLoS ONE 2011, 6(1):e16172.
8. Ferguson B., Matyszak M.K., Esiri M.M., Perry V.H. Axonal damage in acute multiple sclerosis lesions. Brain 1997, 120(Pt 3):393-399.
9. Floris S., et al. Interferon-beta directly influences monocyte infiltration into the central nervous system. J. Neuroimmunol. 2002, 127(1-2):69-79.
10. Ghoreschi K., et al. Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells. J. Exp. Med. 2011, 208(11):2291-2303.
11. Gold R. Combination therapies in multiple sclerosis. J. Neurol. 2008, 255(Suppl. 1):51-60.
12. Gold R., Linington C., Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006, 129(Pt 8):1953-1971.
13. Herrero-Herranz E., Pardo L.A., Gold R., Linker R.A. Pattern of axonal injury in murine myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis: implications for multiple sclerosis. Neurobiol. Dis. 2008, 30(2):162-173.
14. Jacobs L. Magnetic resonance imaging in clinical therapeutic trials of multiple sclerosis. West. J. Med. 1996, 164(6):531-532.
15. Johnson J.A., et al. The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann. N. Y. Acad. Sci. 2008, 1147:61-69.
16. Jolivalt C.G., Howard R.B., Chen L.S., Mizisin A.P., Lai C.S. A novel nitric oxide scavenger in combination with cyclosporine A ameliorates experimental autoimmune encephalomyelitis progression in mice. J. Neuroimmunol. 2003, 138(1-2):56-64.
17. Kieseier B.C. The mechanism of action of interferon-beta in relapsing multiple sclerosis. CNS Drugs 2011, 25(6):491-502.
18. Kornek B., et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am. J. Pathol. 2000, 157(1):267-276.
19. Linker R.A., et al. CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation. Nat. Med. 2002, 8(6):620-624.
20. Linker R.A., et al. EAE in beta-2 microglobulin-deficient mice: axonal damage is not dependent on MHC-I restricted immune responses. Neurobiol. Dis. 2005, 19(1-2):218-228.
21. Linker R.A., et al. Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain 2010, 133(Pt 8):2248-2263.
22. Linker R.A., et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 2011, 134(Pt 3):678-692.
23. Mendes A., Sa M.J. Classical immunomodulatory therapy in multiple sclerosis: how it acts, how it works. Arq. Neuropsiquiatr. 2011, 69(3):536-543.
24. Nelson P.A., et al. Effect of oral beta interferon on subsequent immune responsiveness. Ann. N. Y. Acad. Sci. 1996, 778:145-155.
25. Nikic I., et al. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat. Med. 2011, 17(4):495-499.
26. Prinz M., et al. Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 2008, 28(5):675-686.
27. Ruuls S.R., et al. The length of treatment determines whether IFN-beta prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats. J. Immunol. 1996, 157(12):5721-5731.
28. Scannevin R.H., et al. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J. Pharmacol. Exp. Ther. 2012, 341(1):274-284.
29. Schilling S., Goelz S., Linker R., Luehder F., Gold R. Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration. Clin. Exp. Immunol. 2006, 145(1):101-107.
30. Schmidt J., Sturzebecher S., Toyka K.V., Gold R. Interferon-beta treatment of experimental autoimmune encephalomyelitis leads to rapid nonapoptotic termination of T cell infiltration. J. Neurosci. Res. 2001, 65(1):59-67.
31. Soos J.M., et al. Cutting edge: oral type I IFN-tau promotes a Th2 bias and enhances suppression of autoimmune encephalomyelitis by oral glatiramer acetate. J. Immunol. 2002, 169(5):2231-2235.
32. Trapp B.D., Nave K.A. Multiple sclerosis: an immune or neurodegenerative disorder?. Annu. Rev. Neurosci. 2008, 31:247-269.
33. Trapp B.D., et al. Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 1998, 338(5):278-285.
34. Tuohy V.K., et al. Modulation of the IL-10/IL-12 cytokine circuit by interferon-beta inhibits the development of epitope spreading and disease progression in murine autoimmune encephalomyelitis. J. Neuroimmunol. 2000, 111(1-2):55-63.
35. Vollmer T.L., et al. An open-label safety and drug interaction study of natalizumab (Antegren) in combination with interferon-beta (Avonex) in patients with multiple sclerosis. Mult. Scler. 2004, 10(5):511-520.
36. Weilbach F.X., Chan A., Toyka K.V., Gold R. The cardioprotector dexrazoxane augments therapeutic efficacy of mitoxantrone in experimental autoimmune encephalomyelitis. Clin. Exp. Immunol. 2004, 135(1):49-55.
37. Weiner H.L. The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease?. Ann. Neurol. 2009, 65(3):239-248.
38. Williamson T.P., Johnson D.A., Johnson J.A. Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity. Neurotoxicology 2012, 33(3):272-279.
39. Yamada M., et al. Differences in survival-promoting effects and intracellular signaling properties of BDNF and IGF-1 in cultured cerebral cortical neurons. J. Neurochem. 2001, 78(5):940-951.
40. Yu M., Nishiyama A., Trapp B.D., Tuohy V.K. Interferon-beta inhibits progression of relapsing-remitting experimental autoimmune encephalomyelitis. J. Neuroimmunol. 1996, 64(1):91-100.