[Recent advances in pathogenesis and therapy of multiple sclerosis].

In this article, recent advances in the research on pathogenesis and therapy of multiple sclerosis (MS) will be summarized. New evidence from clinical studies, imaging, histopathology and experimental models are discussed with a focus on neurodegenerative aspects and evidence from recent therapeutic studies. During the last decade, important advances in immunotherapy have been achieved, which proved especially useful for patients with relapsing remitting MS. The introduction of interferons and glatiramer acetate into MS therapy often leads to a stabilization of the disease course if administered adequately and early. The pathogenetic insights presented here may open new avenues for innovative immunomodulatory approaches and lead to an individualized MS therapy in the future. Neuroprotective treatment strategies aim at the protection of glial and neuronal cells.

[1]  H. Maruyama,et al.  Functional , 2020, Congress of Neurological Surgeons Essent.

[2]  C. Stadelmann,et al.  Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis , 2004, Cell Death and Differentiation.

[3]  S. Morrow,et al.  The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis , 2004, Neurology.

[4]  T. Henze,et al.  Symptomatische Therapie der Multiplen Sklerose , 2004, Der Nervenarzt.

[5]  T. Waldmann,et al.  Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  C. Baecher-Allan,et al.  T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis1 , 2004, The Journal of Immunology.

[7]  H. Hartung,et al.  Are statins a treatment option for multiple sclerosis? , 2004, The Lancet Neurology.

[8]  V. Durkalski,et al.  Oral simvastatin treatment in relapsing-remitting multiple sclerosis , 2004, The Lancet.

[9]  D. Bechtold,et al.  Axonal protection using flecainide in experimental autoimmune encephalomyelitis , 2004, Annals of neurology.

[10]  R. Ravid,et al.  Expression of CCR7 in multiple sclerosis: Implications for CNS immunity , 2004, Annals of neurology.

[11]  Clare Baecher-Allan,et al.  Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis , 2004, The Journal of experimental medicine.

[12]  F. Zipp,et al.  Direct Impact of T Cells on Neurons Revealed by Two-Photon Microscopy in Living Brain Tissue , 2004, The Journal of Neuroscience.

[13]  K. Rajewsky,et al.  Multiple sclerosis: brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Nibbering,et al.  Monomethylfumarate affects polarization of monocyte‐derived dendritic cells resulting in down‐regulated Th1 lymphocyte responses , 2004, European journal of immunology.

[15]  G. Freeman,et al.  Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance , 2003, Nature Immunology.

[16]  P. Sørensen,et al.  Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis , 2003, The Lancet.

[17]  Stephen G Waxman,et al.  Temporal Course of Upregulation of Nav1.8 in Purkinje Neurons Parallels the Progression of Clinical Deficit in Experimental Allergic Encephalomyelitis , 2003, Journal of neuropathology and experimental neurology.

[18]  B D Trapp,et al.  Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration , 2003, Multiple sclerosis.

[19]  R. Gold,et al.  Drug targeting by long-circulating liposomal glucocorticosteroids increases therapeutic efficacy in a model of multiple sclerosis. , 2003, Brain : a journal of neurology.

[20]  Stephen G Waxman,et al.  Abnormal sodium channel distribution in optic nerve axons in a model of inflammatory demyelination. , 2003, Brain : a journal of neurology.

[21]  P. Tak,et al.  Gene therapy in nonhuman primate models of human autoimmune disease , 2003, Gene Therapy.

[22]  L. Munari,et al.  Interferons in relapsing remitting multiple sclerosis : a systematic review , 2022 .

[23]  V. Rivera,et al.  Cross‐reactivity with myelin basic protein and human herpesvirus‐6 in multiple sclerosis , 2003, Annals of neurology.

[24]  K. Jellinger,et al.  Preferential Loss of Myelin‐Associated Glycoprotein Reflects Hypoxia‐Like White Matter Damage in Stroke and Inflammatory Brain Diseases , 2003, Journal of neuropathology and experimental neurology.

[25]  H. Hartung,et al.  Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial , 2002, The Lancet.

[26]  P M Matthews,et al.  Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability. , 2002, Brain : a journal of neurology.

[27]  K. Selmaj,et al.  No difference in efficacy of two different doses of intravenous immunoglobulins in MS: clinical and MRI assessment , 2002, European journal of neurology.

[28]  D. Goodkin,et al.  A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis , 2002, Multiple sclerosis.

[29]  Wolfgang Brück,et al.  Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. , 2002, Brain : a journal of neurology.

[30]  Hans Lassmann,et al.  A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. , 2002, Brain : a journal of neurology.

[31]  M. Elices BX-471 Berlex. , 2002, Current opinion in investigational drugs.

[32]  H. Lassmann,et al.  CNTF is a major protective factor in demyelinating CNS disease: A neurotrophic cytokine as modulator in neuroinflammation , 2002, Nature Medicine.

[33]  W. Voelker,et al.  Myocardial function in patients with multiple sclerosis treated with low-dose mitoxantrone. , 2002, The American journal of cardiology.

[34]  A. Ghezzi,et al.  Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN) , 2002, The Lancet.

[35]  R. Gold,et al.  Blockade of signaling via the very late antigen (VLA-4) and its counterligand vascular cell adhesion molecule-1 (VCAM-1) causes increased T cell apoptosis in experimental autoimmune neuritis , 2002, Acta Neuropathologica.

[36]  B. Weinshenker,et al.  Plasma exchange for severe attacks of CNS demyelination: Predictors of response , 2002, Neurology.

[37]  S. Krauss,et al.  Signaling takes a breath--new quantitative perspectives on bioenergetics and signal transduction. , 2001, Immunity.

[38]  B. Trapp,et al.  Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions , 2001, Annals of neurology.

[39]  Lawrence Steinman,et al.  Multiple sclerosis: a two-stage disease , 2001, Nature Immunology.

[40]  M. Bahr,et al.  Acute Neuronal Apoptosis in a Rat Model of Multiple Sclerosis , 2001, The Journal of Neuroscience.

[41]  T. Derfuss,et al.  Intrathecal antibody production against Chlamydia pneumoniae in multiple sclerosis is part of a polyspecific immune response. , 2001, Brain : a journal of neurology.

[42]  A. Compston,et al.  Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis , 2001, Annals of neurology.

[43]  C. Lucchinetti,et al.  A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions , 2001, Annals of neurology.

[44]  H. Lassmann,et al.  Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis. , 2001, Brain : a journal of neurology.

[45]  H. Lassmann,et al.  Migratory activity and functional changes of green fluorescent effector cells before and during experimental autoimmune encephalomyelitis. , 2001, Immunity.

[46]  R. Horuk,et al.  CCR1-specific non-peptide antagonist: efficacy in a rabbit allograft rejection model. , 2001, Immunology letters.

[47]  W. Brück,et al.  Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. , 2000, Brain : a journal of neurology.

[48]  L. Boon,et al.  A new primate model for multiple sclerosis in the common marmoset. , 2000, Immunology today.

[49]  R. Hohlfeld,et al.  Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence. , 2000, Brain : a journal of neurology.

[50]  B. Scheithauer,et al.  A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. , 1999, Brain : a journal of neurology.

[51]  D. MacManus,et al.  The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group. , 1999, Neurology.

[52]  Hans Lassmann,et al.  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? , 1999, The Journal of experimental medicine.

[53]  H. Weiner,et al.  Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia , 1997, Annals of neurology.

[54]  B. Kieseier,et al.  Targets for the therapeutic action of interferon‐β in multiple sclerosis , 1996, Annals of neurology.

[55]  Moses Rodriguez,et al.  Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis , 1996, Brain pathology.

[56]  A. Thompson,et al.  Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. , 1996, Brain : a journal of neurology.

[57]  A. Thompson,et al.  Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. , 1995, Brain : a journal of neurology.

[58]  R. Holmdahl,et al.  Identification of murine loci associated with susceptibility to chronic experimental autoimmune encephalomyelitis , 1995, Nature Genetics.

[59]  K. Jellinger,et al.  Patterns of oligodendroglia pathology in multiple sclerosis. , 1994, Brain : a journal of neurology.

[60]  H. Hartung,et al.  [Cyclophosphamide in therapy of chronic progressive multiple sclerosis. Critical analysis of current studies]. , 1994, Der Nervenarzt.

[61]  H. Webster,et al.  Concentric sclerosis (Baló): Morphometric and in situ hybridization study of lesions in six patients , 1994, Annals of neurology.

[62]  T. Mak,et al.  Less Mortality but More Relapses in Experimental Allergic Encephalomyelitis in CD8-/- Mice , 1992, Science.

[63]  R. Hughes,et al.  Overview of azathioprine treatment in multiple sclerosis , 1991, The Lancet.

[64]  L. Kappos,et al.  Myelin autoreactivity in multiple sclerosis: recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[65]  H. Weiner,et al.  T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis , 1990, Nature.

[66]  W Fierz,et al.  Cyclosporine versus azathioprine in the long‐term treatment of multiple sclerosis—results of the german multicenter study , 1988, Annals of neurology.

[67]  C. Spina Azathioprine as an Immune Modulating Drug: Clinical Applications , 1984, Clinics in Immunology and Allergy.

[68]  T. Rivers,et al.  OBSERVATIONS ON ATTEMPTS TO PRODUCE ACUTE DISSEMINATED ENCEPHALOMYELITIS IN MONKEYS , 1933, The Journal of experimental medicine.

[69]  E. Shevach Regulatory T cells. Introduction. , 2004, Seminars in Immunology.

[70]  高橋 和也 Natural killer type 2 bias in remission of multiple sclerosis , 2003 .

[71]  M. Neurath,et al.  CD 28-dependent Rac 1 activation is the molecular target of azathioprine in primary human CD 4 + T lymphocytes , 2003 .

[72]  Hompson,et al.  A LONGITUDINAL STUDY OF ABNORMALITIES ON MRI AND DISABILITY FROM MULTIPLE SCLEROSIS , 2002 .

[73]  R. Hohlfeld,et al.  Therapeutic approaches in multiple sclerosis: lessons from failed and interrupted treatment trials. , 2002, BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy.

[74]  E. Byrne Randomized, comparative study of interferon beta-1a treatment regimens in MS: the EVIDENCE trial. , 2002, Neurology.

[75]  N. Richert Glatiramer acetate reduces the proportion of new MS lesions evolving into "black holes". , 2002, Neurology.

[76]  P. Rieckmann,et al.  Managing the adverse effects of interferon-beta therapy in multiple sclerosis. , 2000, Drug safety.

[77]  ichard,et al.  AXONAL TRANSECTION IN THE LESIONS OF MULTIPLE SCLEROSIS , 1998 .

[78]  I. Cohen,et al.  The rapid isolation of clonable antigen‐specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis , 1981, European journal of immunology.