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Erschienen in: Journal of Neural Transmission 1/2013

01.09.2013 | Neurology and Preclinical Neurological Studies - Review Article

Advancing therapeutic options in multiple sclerosis with neuroprotective properties

verfasst von: Anke Stroet, Ralf A. Linker, Ralf Gold

Erschienen in: Journal of Neural Transmission | Sonderheft 1/2013

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Abstract

Central nervous system (CNS) inflammation has been considered to be the main pathological feature of multiple sclerosis (MS). However, the complexity of this autoimmune disorder also comprises neurodegenerative processes that may occur within acute phases of inflammation, yet also temporally independent and outside of inflammatory lesions or even in so-called normal appearing white matter. Measurement strategies for neurodegeneration and neuroprotection include clinical parameters, magnetic resonance imaging and novel instruments such as diffusion tensor imaging or optical coherence tomography. Neurotrophic factors activate endogenous neuroprotective pathways. Their up-regulation by CNS-infiltrating immune cells has led to the concept of neuroprotective autoimmunity. The capacity to enhance this endogenous neuroprotection is a valuable property for therapeutic agents and has in detail been studied for glatirameracetate, laquinimod and dimethylfumarate. Multimodal measurement of neuroprotective properties of established and novel MS therapeutics and further elucidation of neuroprotective pathways within the autoimmune process will be useful to augment our insight into the complexity of the disease and to improve therapy, especially in terms of long-term disability and cognitive decline.
Literatur
Zurück zum Zitat Aharoni R, Kayhan B, Eilam R, Sela M, Arnon R (2003) Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ. Proc Natl Acad Sci USA 100(24):14157–14162. doi:10.1073/pnas.2336171100 PubMedCrossRef Aharoni R, Kayhan B, Eilam R, Sela M, Arnon R (2003) Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ. Proc Natl Acad Sci USA 100(24):14157–14162. doi:10.​1073/​pnas.​2336171100 PubMedCrossRef
Zurück zum Zitat Aharoni R, Saada R, Eilam R, Hayardeny L, Sela M, Arnon R (2012) Oral treatment with laquinimod augments regulatory T-cells and brain-derived neurotrophic factor expression and reduces injury in the CNS of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 251(1–2):14–24. doi:10.1016/j.jneuroim.2012.06.005 PubMedCrossRef Aharoni R, Saada R, Eilam R, Hayardeny L, Sela M, Arnon R (2012) Oral treatment with laquinimod augments regulatory T-cells and brain-derived neurotrophic factor expression and reduces injury in the CNS of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 251(1–2):14–24. doi:10.​1016/​j.​jneuroim.​2012.​06.​005 PubMedCrossRef
Zurück zum Zitat Albrecht P, Ringelstein M, Muller AK, Keser N, Dietlein T, Lappas A, Foerster A, Hartung HP, Aktas O, Methner A (2012) Degeneration of retinal layers in multiple sclerosis subtypes quantified by optical coherence tomography. Mult Scler 18(10):1422–1429. doi:10.1177/1352458512439237 PubMedCrossRef Albrecht P, Ringelstein M, Muller AK, Keser N, Dietlein T, Lappas A, Foerster A, Hartung HP, Aktas O, Methner A (2012) Degeneration of retinal layers in multiple sclerosis subtypes quantified by optical coherence tomography. Mult Scler 18(10):1422–1429. doi:10.​1177/​1352458512439237​ PubMedCrossRef
Zurück zum Zitat Altmeyer PJ, Matthes U, Pawlak F, Hoffmann K, Frosch PJ, Ruppert P, Wassilew SW, Horn T, Kreysel HW, Lutz G et al (1994) Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. J Am Acad Dermatol 30(6):977–981PubMedCrossRef Altmeyer PJ, Matthes U, Pawlak F, Hoffmann K, Frosch PJ, Ruppert P, Wassilew SW, Horn T, Kreysel HW, Lutz G et al (1994) Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. J Am Acad Dermatol 30(6):977–981PubMedCrossRef
Zurück zum Zitat Amato MP, Langdon D, Montalban X, Benedict RH, Deluca J, Krupp LB, Thompson AJ, Comi G (2012) Treatment of cognitive impairment in multiple sclerosis: position paper. J Neurol. doi:10.1007/s00415-012-6678-0 PubMed Amato MP, Langdon D, Montalban X, Benedict RH, Deluca J, Krupp LB, Thompson AJ, Comi G (2012) Treatment of cognitive impairment in multiple sclerosis: position paper. J Neurol. doi:10.​1007/​s00415-012-6678-0 PubMed
Zurück zum Zitat Angelov DN, Waibel S, Guntinas-Lichius O, Lenzen M, Neiss WF, Tomov TL, Yoles E, Kipnis J, Schori H, Reuter A, Ludolph A, Schwartz M (2003) Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 100(8):4790–4795. doi:10.1073/pnas.0530191100 PubMedCrossRef Angelov DN, Waibel S, Guntinas-Lichius O, Lenzen M, Neiss WF, Tomov TL, Yoles E, Kipnis J, Schori H, Reuter A, Ludolph A, Schwartz M (2003) Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 100(8):4790–4795. doi:10.​1073/​pnas.​0530191100 PubMedCrossRef
Zurück zum Zitat Avidan H, Kipnis J, Butovsky O, Caspi RR, Schwartz M (2004) Vaccination with autoantigen protects against aggregated beta-amyloid and glutamate toxicity by controlling microglia: effect of CD4+ CD25+ T cells. Eur J Immunol 34(12):3434–3445. doi:10.1002/eji.200424883 PubMedCrossRef Avidan H, Kipnis J, Butovsky O, Caspi RR, Schwartz M (2004) Vaccination with autoantigen protects against aggregated beta-amyloid and glutamate toxicity by controlling microglia: effect of CD4+ CD25+ T cells. Eur J Immunol 34(12):3434–3445. doi:10.​1002/​eji.​200424883 PubMedCrossRef
Zurück zum Zitat Barres BA (1996) Ciliary neurotrophic factor enhances the rate of oligodendrocyte generation. Mol Cell Neurosci 8:146–156CrossRef Barres BA (1996) Ciliary neurotrophic factor enhances the rate of oligodendrocyte generation. Mol Cell Neurosci 8:146–156CrossRef
Zurück zum Zitat Bruck W, Pfortner R, Pham T, Zhang J, Hayardeny L, Piryatinsky V, Hanisch UK, Regen T, van Rossum D, Brakelmann L, Hagemeier K, Kuhlmann T, Stadelmann C, John GR, Kramann N, Wegner C (2012) Reduced astrocytic NF-kappaB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol 124(3):411–424. doi:10.1007/s00401-012-1009-1 PubMedCrossRef Bruck W, Pfortner R, Pham T, Zhang J, Hayardeny L, Piryatinsky V, Hanisch UK, Regen T, van Rossum D, Brakelmann L, Hagemeier K, Kuhlmann T, Stadelmann C, John GR, Kramann N, Wegner C (2012) Reduced astrocytic NF-kappaB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol 124(3):411–424. doi:10.​1007/​s00401-012-1009-1 PubMedCrossRef
Zurück zum Zitat Davie CA, Barker GJ, Webb S, Tofts PS, Thompson AJ, Harding AE, McDonald WI, Miller DH (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118(Pt 6):1583–1592PubMedCrossRef Davie CA, Barker GJ, Webb S, Tofts PS, Thompson AJ, Harding AE, McDonald WI, Miller DH (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118(Pt 6):1583–1592PubMedCrossRef
Zurück zum Zitat De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS, Antel JP, Arnold DL (1998) Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121(Pt 8):1469–1477PubMedCrossRef De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS, Antel JP, Arnold DL (1998) Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121(Pt 8):1469–1477PubMedCrossRef
Zurück zum Zitat Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT (2012) Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 367(12):1087–1097. doi:10.1056/NEJMoa1206328 PubMedCrossRef Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT (2012) Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 367(12):1087–1097. doi:10.​1056/​NEJMoa1206328 PubMedCrossRef
Zurück zum Zitat Frohman EM, Fujimoto JG, Frohman TC, Calabresi PA, Cutter G, Balcer LJ (2008) Optical coherence tomography: a window into the mechanisms of multiple sclerosis. Nat Clin Pract Neurol 4(12):664–675. doi:10.1038/ncpneuro0950 PubMedCrossRef Frohman EM, Fujimoto JG, Frohman TC, Calabresi PA, Cutter G, Balcer LJ (2008) Optical coherence tomography: a window into the mechanisms of multiple sclerosis. Nat Clin Pract Neurol 4(12):664–675. doi:10.​1038/​ncpneuro0950 PubMedCrossRef
Zurück zum Zitat Gold R, Linington C, Lassmann H (2006) Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129(Pt 8):1953–1971. doi:10.1093/brain/awl075 PubMedCrossRef Gold R, Linington C, Lassmann H (2006) Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129(Pt 8):1953–1971. doi:10.​1093/​brain/​awl075 PubMedCrossRef
Zurück zum Zitat Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT (2012) Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 367(12):1098–1107. doi:10.1056/NEJMoa1114287 PubMedCrossRef Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT (2012) Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 367(12):1098–1107. doi:10.​1056/​NEJMoa1114287 PubMedCrossRef
Zurück zum Zitat Goodin DS, Ebers GC, Cutter G, Cook SD, O’Donnell T, Reder AT, Kremenchutzky M, Oger J, Rametta M, Beckmann K, Knappertz V (2012) Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFNbeta-1b study. BMJ Open 2(6). doi:10.1136/bmjopen-2012-001972 Goodin DS, Ebers GC, Cutter G, Cook SD, O’Donnell T, Reder AT, Kremenchutzky M, Oger J, Rametta M, Beckmann K, Knappertz V (2012) Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFNbeta-1b study. BMJ Open 2(6). doi:10.​1136/​bmjopen-2012-001972
Zurück zum Zitat Gorantla S, Liu J, Sneller H, Dou H, Holguin A, Smith L, Ikezu T, Volsky DJ, Poluektova L, Gendelman HE (2007) Copolymer-1 induces adaptive immune anti-inflammatory glial and neuroprotective responses in a murine model of HIV-1 encephalitis. J Immunol 179(7):4345–4356PubMed Gorantla S, Liu J, Sneller H, Dou H, Holguin A, Smith L, Ikezu T, Volsky DJ, Poluektova L, Gendelman HE (2007) Copolymer-1 induces adaptive immune anti-inflammatory glial and neuroprotective responses in a murine model of HIV-1 encephalitis. J Immunol 179(7):4345–4356PubMed
Zurück zum Zitat Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde YA (1990) Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J 9(8):2459–2464PubMed Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde YA (1990) Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J 9(8):2459–2464PubMed
Zurück zum Zitat Hohlfeld R, Wekerle H (2004) Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines. Proc Natl Acad Sci USA 101(Suppl 2):14599–14606. doi:10.1073/pnas.0404874101 PubMedCrossRef Hohlfeld R, Wekerle H (2004) Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines. Proc Natl Acad Sci USA 101(Suppl 2):14599–14606. doi:10.​1073/​pnas.​0404874101 PubMedCrossRef
Zurück zum Zitat Hulst HE, Steenwijk MD, Versteeg A, Pouwels PJ, Vrenken H, Uitdehaag BM, Polman CH, Geurts JJ, Barkhof F (2013) Cognitive impairment in MS: impact of white matter integrity, gray matter volume, and lesions. Neurology. doi:10.1212/WNL.0b013e31828726cc PubMed Hulst HE, Steenwijk MD, Versteeg A, Pouwels PJ, Vrenken H, Uitdehaag BM, Polman CH, Geurts JJ, Barkhof F (2013) Cognitive impairment in MS: impact of white matter integrity, gray matter volume, and lesions. Neurology. doi:10.​1212/​WNL.​0b013e31828726cc​ PubMed
Zurück zum Zitat Kappos L, Gold R, Miller DH, Macmanus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, Eraksoy M, Meluzinova E, Rektor I, Dawson KT, Sandrock AW, O’Neill GN (2008) Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 372(9648):1463–1472. doi:10.1016/S0140-6736(08)61619-0 PubMedCrossRef Kappos L, Gold R, Miller DH, Macmanus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, Eraksoy M, Meluzinova E, Rektor I, Dawson KT, Sandrock AW, O’Neill GN (2008) Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 372(9648):1463–1472. doi:10.​1016/​S0140-6736(08)61619-0 PubMedCrossRef
Zurück zum Zitat Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189(5):865–870PubMedCrossRef Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189(5):865–870PubMedCrossRef
Zurück zum Zitat Kipnis J, Schwartz M (2002) Dual action of glatiramer acetate (Cop-1) in the treatment of CNS autoimmune and neurodegenerative disorders. Trends Mol Med 8(7):319–323PubMedCrossRef Kipnis J, Schwartz M (2002) Dual action of glatiramer acetate (Cop-1) in the treatment of CNS autoimmune and neurodegenerative disorders. Trends Mol Med 8(7):319–323PubMedCrossRef
Zurück zum Zitat Linker RA, Maurer M, Gaupp S, Martini R, Holtmann B, Giess R, Rieckmann P, Lassmann H, Toyka KV, Sendtner M, Gold R (2002) CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation. Nat Med 8(6):620–624. doi:10.1038/nm0602-620 PubMedCrossRef Linker RA, Maurer M, Gaupp S, Martini R, Holtmann B, Giess R, Rieckmann P, Lassmann H, Toyka KV, Sendtner M, Gold R (2002) CNTF is a major protective factor in demyelinating CNS disease: a neurotrophic cytokine as modulator in neuroinflammation. Nat Med 8(6):620–624. doi:10.​1038/​nm0602-620 PubMedCrossRef
Zurück zum Zitat Linker RA, Lee DH, Demir S, Wiese S, Kruse N, Siglienti I, Gerhardt E, Neumann H, Sendtner M, Luhder F, Gold R (2010) Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain 133(Pt 8):2248–2263. doi:10.1093/brain/awq179 PubMedCrossRef Linker RA, Lee DH, Demir S, Wiese S, Kruse N, Siglienti I, Gerhardt E, Neumann H, Sendtner M, Luhder F, Gold R (2010) Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain 133(Pt 8):2248–2263. doi:10.​1093/​brain/​awq179 PubMedCrossRef
Zurück zum Zitat Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, Zeng W, Hronowsky X, Buko A, Chollate S, Ellrichmann G, Bruck W, Dawson K, Goelz S, Wiese S, Scannevin RH, Lukashev M, Gold R (2011) Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 134(Pt 3):678–692. doi:10.1093/brain/awq386 PubMedCrossRef Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, Zeng W, Hronowsky X, Buko A, Chollate S, Ellrichmann G, Bruck W, Dawson K, Goelz S, Wiese S, Scannevin RH, Lukashev M, Gold R (2011) Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 134(Pt 3):678–692. doi:10.​1093/​brain/​awq386 PubMedCrossRef
Zurück zum Zitat Louis JC, Magal E, Takayama S, Varon S (1993) CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 259:689–692PubMedCrossRef Louis JC, Magal E, Takayama S, Varon S (1993) CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 259:689–692PubMedCrossRef
Zurück zum Zitat Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46(4):907–911PubMedCrossRef Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46(4):907–911PubMedCrossRef
Zurück zum Zitat Lukas C, Minneboo A, de Groot V, Moraal B, Knol DL, Polman CH, Barkhof F, Vrenken H (2010) Early central atrophy rate predicts 5 year clinical outcome in multiple sclerosis. J Neurol Neurosurg Psychiatry 81(12):1351–1356. doi:10.1136/jnnp.2009.199968 PubMedCrossRef Lukas C, Minneboo A, de Groot V, Moraal B, Knol DL, Polman CH, Barkhof F, Vrenken H (2010) Early central atrophy rate predicts 5 year clinical outcome in multiple sclerosis. J Neurol Neurosurg Psychiatry 81(12):1351–1356. doi:10.​1136/​jnnp.​2009.​199968 PubMedCrossRef
Zurück zum Zitat Nieboer C, de Hoop D, Langendijk PN, van Loenen AC, Gubbels J (1990) Fumaric acid therapy in psoriasis: a double-blind comparison between fumaric acid compound therapy and monotherapy with dimethylfumaric acid ester. Dermatologica 181(1):33–37PubMedCrossRef Nieboer C, de Hoop D, Langendijk PN, van Loenen AC, Gubbels J (1990) Fumaric acid therapy in psoriasis: a double-blind comparison between fumaric acid compound therapy and monotherapy with dimethylfumaric acid ester. Dermatologica 181(1):33–37PubMedCrossRef
Zurück zum Zitat Papadopoulou A, Muller-Lenke N, Naegelin Y, Kalt G, Bendfeldt K, Kuster P, Stoecklin M, Gass A, Sprenger T, Wilhelm Radue E, Kappos L, Penner IK (2013) Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler. doi:10.1177/1352458513475490 Papadopoulou A, Muller-Lenke N, Naegelin Y, Kalt G, Bendfeldt K, Kuster P, Stoecklin M, Gass A, Sprenger T, Wilhelm Radue E, Kappos L, Penner IK (2013) Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis. Mult Scler. doi:10.​1177/​1352458513475490​
Zurück zum Zitat Penner IK, Stemper B, Calabrese P, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Pleimes D, Lanius V, Pohl C, Kappos L, Sandbrink R (2012) Effects of interferon beta-1b on cognitive performance in patients with a first event suggestive of multiple sclerosis. Mult Scler 18(10):1466–1471. doi:10.1177/1352458512442438 PubMedCrossRef Penner IK, Stemper B, Calabrese P, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, Montalban X, Barkhof F, Pleimes D, Lanius V, Pohl C, Kappos L, Sandbrink R (2012) Effects of interferon beta-1b on cognitive performance in patients with a first event suggestive of multiple sclerosis. Mult Scler 18(10):1466–1471. doi:10.​1177/​1352458512442438​ PubMedCrossRef
Zurück zum Zitat Petzold A, de Boer JF, Schippling S, Vermersch P, Kardon R, Green A, Calabresi PA, Polman C (2010) Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol 9(9):921–932. doi:10.1016/S1474-4422(10)70168-X PubMedCrossRef Petzold A, de Boer JF, Schippling S, Vermersch P, Kardon R, Green A, Calabresi PA, Polman C (2010) Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol 9(9):921–932. doi:10.​1016/​S1474-4422(10)70168-X PubMedCrossRef
Zurück zum Zitat Rovaris M, Filippi M, Minicucci L, Iannucci G, Santuccio G, Possa F, Comi G (2000) Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis. AJNR 21(2):402–408PubMed Rovaris M, Filippi M, Minicucci L, Iannucci G, Santuccio G, Possa F, Comi G (2000) Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis. AJNR 21(2):402–408PubMed
Zurück zum Zitat Schimrigk S, Brune N, Hellwig K, Lukas C, Bellenberg B, Rieks M, Hoffmann V, Pohlau D, Przuntek H (2006) Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study. Eur J Neurology 13(6):604–610. doi:10.1111/j.1468-1331.2006.01292.x CrossRef Schimrigk S, Brune N, Hellwig K, Lukas C, Bellenberg B, Rieks M, Hoffmann V, Pohlau D, Przuntek H (2006) Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study. Eur J Neurology 13(6):604–610. doi:10.​1111/​j.​1468-1331.​2006.​01292.​x CrossRef
Zurück zum Zitat Schweckendiek W (1959) Treatment of psoriasis vulgaris. Medizinische Monatsschrift 13(2):103–104PubMed Schweckendiek W (1959) Treatment of psoriasis vulgaris. Medizinische Monatsschrift 13(2):103–104PubMed
Zurück zum Zitat Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann H (2002) BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125(Pt 1):75–85PubMedCrossRef Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann H (2002) BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125(Pt 1):75–85PubMedCrossRef
Zurück zum Zitat Thone J, Ellrichmann G, Seubert S, Peruga I, Lee DH, Conrad R, Hayardeny L, Comi G, Wiese S, Linker RA, Gold R (2012) Modulation of autoimmune demyelination by laquinimod via induction of brain-derived neurotrophic factor. Am J Pathol 180(1):267–274. doi:10.1016/j.ajpath.2011.09.037 PubMedCrossRef Thone J, Ellrichmann G, Seubert S, Peruga I, Lee DH, Conrad R, Hayardeny L, Comi G, Wiese S, Linker RA, Gold R (2012) Modulation of autoimmune demyelination by laquinimod via induction of brain-derived neurotrophic factor. Am J Pathol 180(1):267–274. doi:10.​1016/​j.​ajpath.​2011.​09.​037 PubMedCrossRef
Zurück zum Zitat Ziemssen T, Kumpfel T, Klinkert WE, Neuhaus O, Hohlfeld R (2002) Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor. Brain 125(Pt 11):2381–2391PubMedCrossRef Ziemssen T, Kumpfel T, Klinkert WE, Neuhaus O, Hohlfeld R (2002) Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor. Brain 125(Pt 11):2381–2391PubMedCrossRef
Metadaten
Titel
Advancing therapeutic options in multiple sclerosis with neuroprotective properties
verfasst von
Anke Stroet
Ralf A. Linker
Ralf Gold
Publikationsdatum
01.09.2013
Verlag
Springer Vienna
Erschienen in
Journal of Neural Transmission / Ausgabe Sonderheft 1/2013
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-013-1037-6

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