Targeting progressive neuroaxonal injury: Lessons from multiple sclerosis

CNS Drugs

Volumn 25, Issue 9, 2011, Pages 783-799

  Bar Or, Amit ^a   Rieckmann, Peter ^b   Traboulsee, Anthony ^c   Yong, V Wee ^d  

^a MCGILL UNIVERSITY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^d UNIVERSITY OF CALGARY   (Canada)

Author keywords

Alzheimers disease; Amyotrophic lateral sclerosis; Glatiramer acetate; Interferon beta; Multiple sclerosis; Neurodegenerative disorders; Parkinsons disease.

Indexed keywords

ALPHA SYNUCLEIN; AUTOANTIBODY; BETA INTERFERON; BETA1A INTERFERON; GADOLINIUM; GLATIRAMER; IBUDILAST; INTERFERON BETA SERINE; IRON; LAMOTRIGINE; MITOXANTRONE; NATALIZUMAB; PLACEBO; TAU PROTEIN;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANTIGEN PRESENTING CELL; ANTIINFLAMMATORY ACTIVITY; AXONAL INJURY; BRAIN ATROPHY; CONTRAST ENHANCEMENT; DEGENERATIVE DISEASE; DIAGNOSTIC TEST; DIFFUSION TENSOR IMAGING; DISEASE COURSE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG EFFECT; HUMAN; INFLAMMATION; IRON DEFICIENCY; MAGNETIZATION TRANSFER RATION; MICROGLIA; MITOCHONDRION; MULTIPLE SCLEROSIS; MYELIN WATER IMAGING; NERVE DEGENERATION; NERVE REGENERATION; NERVOUS SYSTEM DEVELOPMENT; NEUROAXONAL INJURY; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OPTIC NERVE; OPTICAL COHERENCE TOMOGRAPHY; PARKINSON DISEASE; PATHOGENESIS; PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS; PRIORITY JOURNAL; RETINA GANGLION CELL; REVIEW; SPINAL CORD ATROPHY;

ANIMALS; CLINICAL TRIALS, PHASE II AS TOPIC; DISEASE PROGRESSION; HUMANS; MULTIPLE SCLEROSIS; NEURODEGENERATIVE DISEASES; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 80052138366     PISSN: 11727047     EISSN: 11791934     Source Type: Journal    
DOI: 10.2165/11587820-000000000-00000     Document Type: Review

References (116)

1. Gibb WR. Neuropathology of Parkinson's disease and related syndromes. Neurol Clin 1992 May; 10 (2): 361-76
2. Sperling R, Johnson K. Pro: can biomarkers be gold standards in Alzheimer's disease [abstract]? Alzheimers Res Ther 2010 Jun 25; 2 (3): 17
3. Pahwa R, Lyons KE. Early diagnosis of Parkinson's disease: recommendations from diagnostic clinical guidelines. Am J Manag Care 2010 Mar; 16 Suppl Implications: S94-9
4. Olanow CW, Schapira AH, LeWitt PA, et al. TCH346 as a neuroprotective drug in Parkinson's disease: a doubleblind, randomised, controlled trial. Lancet Neurol 2006 Dec; 5 (12): 1013-20 (Pubitemid 44709968)
5. Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. J Neurochem 1998 May; 70 (5): 1781-92 (Pubitemid 28207799)
6. Kieburtz K. Issues in neuroprotection clinical trials in Parkinson's disease. Neurology 2006May 23; 66 (10 Suppl. 4): S50-7
7. Slikkker W, Youdim M, Palmer GC, et al. The future of neuroprotection. Ann N Y Acad Sci 1999; 890: 529-33 (Pubitemid 30040418)
8. Confavreux C, Vukusic S. Age at disability milestones in multiple sclerosis. Brain 2006 Mar; 129 (Pt 3): 595-605 (Pubitemid 43278222)
9. Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain 2006 Mar; 129 (Pt 3): 606-16 (Pubitemid 43278223)
10. Bar-Or A. The immunology of multiple sclerosis. Semin Neurol 2008 Feb; 28 (1): 29-45 (Pubitemid 351273082)
11. Hemmer B, Nessler S, Zhou D, et al. Immunopathogenesis and immunotherapy of multiple sclerosis. Nat Clin Pract Neurol 2006 Apr; 2 (4): 201-11
12. Martino G, Adorini L, Rieckmann P, et al. Inflammation in multiple sclerosis: the good, the bad, and the complex. Lancet Neurol 2002 Dec; 1 (8): 499-509 (Pubitemid 37159141)
13. McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 2007 Sep; 8 (9): 913-9 (Pubitemid 47300005)
14. Kutzelnigg A, Lucchinetti CF, Stadelmann C, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005 Nov; 128 (Pt 11): 2705-12 (Pubitemid 41552953)
15. Li DK, ZhaoGJ, Paty DW. Randomized controlled trial of interferon-beta-1a in secondary progressive MS: MRI results. Neurology 2001 Jun 12; 56 (11): 1505-13 (Pubitemid 32532262)
16. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferonbeta-1a in secondary progressive MS: clinical results. Neurology 2001 Jun 12; 56 (11): 1496-504
17. Truyen L, van Waesberghe JH, van Walderveen MA, et al. Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis. Neurology 1996 Dec; 47 (6): 1469-76 (Pubitemid 26422538)
18. FilippiM, Rovaris M, Rocca MA, et al. Glatiramer acetate reduces the proportion of new MS lesions evolving into "black holes". Neurology 2001 Aug 28; 57 (4): 731-3 (Pubitemid 32783013)
19. Chard DT, Griffin CM, McLean MA, et al. Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis. Brain 2002 Oct; 125 (Pt 10): 2342-52
20. De Stefano N, Narayanan S, Francis SJ, et al. Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability. Arch Neurol 2002 Oct; 59 (10): 1565-71
21. Bjartmar C, Kidd G, Mork S, et al. Neurological disability correlates with spinal cord axonal loss and reduced Nacetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 2000 Dec; 48 (6): 893-901
22. Sepulcre J, Sastre-Garriga J, CercignaniM, et al. Regional gray matter atrophy in early primary progressive multiple sclerosis: a voxel-based morphometry study. Arch Neurol 2006 Aug; 63 (8): 1175-80 (Pubitemid 44232328)
23. Rashid W, Davies GR, Chard DT, et al. Increasing cord atrophy in early relapsing-remitting multiple sclerosis: a 3 year study. J Neurol Neurosurg Psychiatry 2006 Jan; 77 (1): 51-5 (Pubitemid 43022690)
24. Martino G. How the brain repairs itself: new therapeutic strategies in inflammatory and degenerative CNS disorders. Lancet Neurol 2004 Jun; 3 (6): 372-8 (Pubitemid 38648859)
25. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 2008; 31: 247-69
26. Dhib-Jalbut S, Arnold DL, Cleveland DW, et al. Neurodegeneration and neuroprotection in multiple sclerosis and other neurodegenerative diseases. J Neuroimmunol 2006 Jul; 176 (1-2): 198-215 (Pubitemid 44080333)
27. Trapp BD, Stys PK. Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol 2009; 8: 280-91
28. Craner MJ, Newcombe J, Black JA, et al. Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger. Proc Natl Acad Sci USA 2004 May 25; 101 (21): 8168-73 (Pubitemid 38698072)
29. Smith KJ, McDonald WI. The pathophysiology of multiple sclerosis: the mechanisms underlying the production of symptoms and the natural history of the disease. Philos Trans R Soc Lond B Biol Sci 1999 Oct 29; 354 (1390): 1649-73 (Pubitemid 29534432)
30. Hohlfeld R. Biotechnological agents for the immunotherapy of multiple sclerosis: principles, problems and perspectives. Brain 1997 May; 120 (Pt 5): 865-916
31. Dutta G, Zhang P, Liu B. The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and drug discovery. Fundam Clin Pharmacol 2008 Oct; 22 (5): 453-64
32. Wu DC, Re DB, Nagai M, et al. The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Proc Natl Acad Sci USA 2006 Aug 8; 103 (32): 12132-7 (Pubitemid 44215823)
33. Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer's disease. Neurobiol Aging 2000 May-Jun; 21 (3): 383-421 (Pubitemid 30349107)
34. Owens T. The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage. Curr Opin Neurol 2003 Jun; 16 (3): 259-65 (Pubitemid 36688291)
35. Lu JQ, Fan Y, Mitha AP, et al. Association of alphasynuclein immunoreactivity with inflammatory activity in multiple sclerosis lesions. J Neuropathol Exp Neurol 2009 Feb; 68 (2): 179-89
36. Holtzer R, Irizarry MC, Sanders J, et al. Relation of quantitative indexes of concurrent alpha-synuclein abnormalities to clinical outcome in autopsy-proven Alzheimer disease. Arch Neurol 2006 Feb; 63 (2): 226-30 (Pubitemid 43261734)
37. Zhang W, Wang T, Pei Z, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J 2005 Apr; 19 (6): 533-42 (Pubitemid 40471244)
38. Hedegaard CJ, Chen N, Sellebjerg F, et al. Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP. Immunology 2009 Sep; 128 (1 Suppl.): e451-61
39. Kellner A, Matschke J, Bernreuther C, et al. Autoantibodies against beta-amyloid are common in Alzheimer's disease and help control plaque burden. Ann Neurol 2009 Jan; 65 (1): 24-31
40. Couratier P, Yi FH, Preud'homme JL, et al. Serum autoantibodies to neurofilament proteins in sporadic amyotrophic lateral sclerosis. J Neurol Sci 1998 Feb 5; 154 (2): 137-45 (Pubitemid 28156929)
41. Papachroni KK, Ninkina N, Papapanagiotou A, et al. Autoantibodies to alpha-synuclein in inherited Parkinson's disease. J Neurochem 2007 May; 101 (3): 749-56 (Pubitemid 46633311)
42. Haacke EM, Makki M, Ge Y, et al. Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging. J Magn Reson Imaging 2009 Mar; 29 (3): 537-44
43. Collingwood JF, Chong RK, Kasama T, et al. Threedimensional tomographic imaging and characterization of iron compounds within Alzheimer's plaque core material. J Alzheimers Dis 2008 Jun; 14 (2): 235-45 (Pubitemid 352040039)
44. Jeong SY, Rathore KI, Schulz K, et al. Dysregulation of iron homeostasis in the CNS contributes to disease progression in a mouse model of amyotrophic lateral sclerosis. J Neurosci 2009 Jan 21; 29 (3): 610-9
45. Bartzokis G, Lu PH, Tishler TA, et al. Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Neurochem Res 2007 Oct; 32 (10): 1655-64 (Pubitemid 47428858)
46. Wallis LI, Paley MN, Graham JM, et al. MRI assessment of basal ganglia iron deposition in Parkinson's disease. J Magn Reson Imaging 2008 Nov; 28 (5): 1061-7
47. Rasmussen S,Wang Y, Kivisakk P, et al. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing-remitting experimental autoimmune encephalomyelitis. Brain 2007 Nov; 130 (Pt 11): 2816-29 (Pubitemid 350033966)
48. Streit WJ.Microglia and neuroprotection: implications for Alzheimer's disease. Brain Res Brain Res Rev 2005 Apr; 48 (2): 234-9 (Pubitemid 40585754)
49. Sargsyan SA, Monk PN, Shaw PJ. Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis. Glia 2005 Sep; 51 (4): 241-53 (Pubitemid 41532100)
50. Dutta R, McDonough J, Yin X, et al. Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol 2006 Mar; 59 (3): 478-89 (Pubitemid 43358068)
51. Leuner K, Pantel J, Frey C, et al. Enhanced apoptosis, oxidative stress and mitochondrial dysfunction in lymphocytes as potential biomarkers for Alzheimer's disease. J Neural Transm Suppl 2007; 72: 207-15
52. Oliveira JM, Jekabsons MB, Chen S, et al. Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice. J Neurochem 2007 Apr; 101 (1): 241-9 (Pubitemid 46426480)
53. Stack EC, Ferro JL, Kim J, et al. Therapeutic attenuation of mitochondrial dysfunction and oxidative stress in neurotoxin models of Parkinson's disease. Biochim Biophys Acta 2008 Mar; 1782 (3): 151-62
54. Anderson JM, Hampton DW, Patani R, et al. Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis. Brain 2008 Jul; 131 (Pt 7): 1736-48 (Pubitemid 351957465)
55. Terzi M, Birinci A, Cetinkaya E, et al. Cerebrospinal fluid total tau protein levels in patients with multiple sclerosis. Acta Neurol Scand 2007 May; 115 (5): 325-30 (Pubitemid 46699430)
56. Hampel H, Teipel SJ, Fuchsberger T, et al. Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. Mol Psychiatry 2004 Jul; 9 (7): 705-10 (Pubitemid 38932175)
57. Gohar M, Yang W, Strong W, et al. Tau phosphorylation at threonine-175 leads to fibril formation and enhanced cell death: implications for amyotrophic lateral sclerosis with cognitive impairment. J Neurochem 2009 Feb; 108 (3): 634-43
58. Berg D, Youdim MB. Role of iron in neurodegenerative disorders. Top Magn Reson Imaging 2006 Feb; 17 (1): 5-17 (Pubitemid 46672929)
59. Rego AC, Oliveira CR. Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochem Res 2003 Oct; 28 (10): 1563-74 (Pubitemid 37193539)
60. Venkateswaran S, Banwell B. Pediatric multiple sclerosis. Neurologist 2010 Mar; 16 (2): 92-105
61. Dev KK, Hofele K, Barbieri S, et al. Part II: alphasynuclein and its molecular pathophysiological role in neurodegenerative disease. Neuropharmacology 2003 Jul; 45 (1): 14-44 (Pubitemid 36695009)
62. Williams DR. Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubuleassociated protein tau. Intern Med J 2006 Oct; 36 (10): 652-60 (Pubitemid 44337509)
63. Elkon K, Casali P. Nature and functions of autoantibodies. Nat Clin Pract Rheumatol 2008 Sep; 4 (9): 491-8
64. Neumann H, Kotter MR, Franklin RJ.Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 2009 Feb; 132 (Pt 2): 288-95
65. Bakshi R, Thompson AJ, Rocca MA, et al. MRI in multiple sclerosis: current status and future prospects. Lancet Neurol 2008 Jul; 7 (7): 615-25
66. Schuff N, Woerner N, Boreta L, et al. MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers. Brain 2009 Apr; 132 (Pt 4): 1067-77
67. Fisher E, Rudick RA, Simon JH, et al. Eight-year followup study of brain atrophy in patients with MS. Neurology 2002 Nov 12; 59 (9): 1412-20 (Pubitemid 35285996)
68. Khan O. Can clinical outcomes be used to detect neuroprotection in multiple sclerosis? Neurology 2007 May 29; 68 (22 Suppl. 3): S64-71; discussion S91-6
69. Daumer M, Neuhaus A, Morrissey S, et al. MRI as an outcome in multiple sclerosis clinical trials. Neurology 2009 Feb 24; 72 (8): 705-11
70. Sormani MP, Bonzano L, Roccatagliata L, et al. Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: a meta-analytic approach. Ann Neurol 2009 Mar; 65 (3): 268-75
71. Laule C, Kozlowski P, Leung E, et al. Myelin water imaging of multiple sclerosis at 7 T: correlations with histopathology. Neuroimage 2008 May 1; 40 (4): 1575-80
72. Chen JT, Collins DL, Atkins HL, et al. Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesions. Ann Neurol 2008 Feb; 63 (2): 254-62 (Pubitemid 351355304)
73. Geurts JJ, Barkhof F. Grey matter pathology in multiple sclerosis. Lancet Neurol 2008 Sep; 7 (9): 841-51
74. Kutzelnigg A, Lassmann H. Cortical demyelination in multiple sclerosis: a substrate for cognitive deficits? J Neurol Sci 2006 Jun 15; 245 (1-2): 123-6 (Pubitemid 43775930)
75. Simmons A, Westman E, Muehlboeck S, et al. MRI measures of Alzheimer's disease and the AddNeuroMed study. Ann N Y Acad Sci 2009 Oct; 1180: 47-55
76. Beyer MK, Janvin CC, Larsen JP, et al. A magnetic resonance imaging study of patients with Parkinson's disease with mild cognitive impairment and dementia using voxel-based morphometry. J Neurol Neurosurg Psychiatry 2007 Mar; 78 (3): 254-9 (Pubitemid 46579662)
77. Reetz K, Gaser C, Klein C, et al. Structural findings in the basal ganglia in genetically determined and idiopathic Parkinson's disease.Mov Disord 2009 Jan 15; 24 (1): 99-103
78. Agosta F, Rocca MA, Valsasina P, et al. A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients. J Neurol Neurosurg Psychiatry 2009 Jan; 80 (1): 53-5
79. Grosskreutz J, Peschel T, Unrath A, et al. Whole brainbased computerized neuroimaging in ALS and other motor neuron disorders. Amyotroph Lateral Scler 2008 Aug; 9 (4): 238-48
80. Ginestroni A, Battaglini M, Della Nave R, et al. Early structural changes in individuals at risk of familial Alzheimer's disease: a volumetry and magnetization transfer MR imaging study. J Neurol 2009 Jun; 256 (6): 925-32
81. Kiefer C, Brockhaus L, Cattapan-Ludewig K, et al. Multiparametric classification of Alzheimer's disease and mild cognitive impairment: the impact of quantitative magnetization transfer MR imaging. Neuroimage 2009 Dec; 48 (4): 657-67
82. Ridha BH, Tozer DJ, Symms MR, et al. Quantitative magnetization transfer imaging in Alzheimer disease. Radiology 2007 Sep; 244 (3): 832-7 (Pubitemid 47292095)
83. van Es AC, van der Flier WM, Admiraal-Behloul F, et al. Lobar distribution of changes in gray matter and white matter in memory clinic patients: detected using magnetization transfer imaging. Am J Neuroradiol 2007 Nov-Dec; 28 (10): 1938-42 (Pubitemid 350174739)
84. Anik Y, Iseri P, Demirci A, et al. Magnetization transfer ratio in early period of Parkinson disease. Acad Radiol 2007 Feb; 14 (2): 189-92 (Pubitemid 46127652)
85. Eckert T, Sailer M, Kaufmann J, et al. Differentiation of idiopathic Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and healthy controls using magnetization transfer imaging. Neuroimage 2004 Jan; 21 (1): 229-35 (Pubitemid 38115013)
86. Tambasco N, Pelliccioli GP, Chiarini P, et al. Magnetization transfer changes of grey and white matter in Parkinson's disease. Neuroradiology 2003 Apr; 45 (4): 224-30 (Pubitemid 36700847)
87. Andjus PR, Bataveljic D, Vanhoutte G, et al. In vivo morphological changes in animal models of amyotrophic lateral sclerosis and Alzheimer's-like disease: MRI approach. Anat Rec (Hoboken) 2009 Dec; 292 (12): 1882-92
88. Santillo AF, Skoglund L, Lindau M, et al. Frontotemporal dementia-amyotrophic lateral sclerosis complex is simulated by neurodegeneration with brain iron accumulation. Alzheimer Dis Assoc Disord 2009 Jul-Sep; 23 (3): 298-300
89. Frohman EM, Fujimoto JG, Frohman TC, et al. Optical coherence tomography: a window into the mechanisms of multiple sclerosis. Nat Clin Pract Neurol 2008 Dec; 4 (12): 664-75
90. Costello F, Hodge W, Pan YI, et al. Tracking retinal nerve fiber layer loss after optic neuritis: a prospective study using optical coherence tomography. Mult Scler 2008 Aug; 14 (7): 893-905
91. Inglese M, Mancardi GL, Pagani E, et al. Brain tissue loss occurs after suppression of enhancement in patients with multiple sclerosis treated with autologous haematopoietic stem cell transplantation. J Neurol Neurosurg Psychiatry 2004 Apr; 75 (4): 643-4 (Pubitemid 38406670)
92. Boutros T, Croze E, Yong VW. Interferon-beta is a potent promoter of nerve growth factor production by astrocytes. J Neurochem 1997 Sep; 69 (3): 939-46 (Pubitemid 27364813)
93. Kapoor R, Furby J, Hayton T, et al. Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Neurol 2010 Jul; 9 (7): 681-8
94. Barkhof F, Hulst HE, Drulovic J, et al. Ibudilast in relapsingremitting multiple sclerosis: a neuroprotectant? Neurology 2010 Mar 30; 74 (13): 1033-40
95. Antel JP, Miron VE. Central nervous system effects of current and emerging multiple sclerosis-directed immuno-therapies. Clin Neurol Neurosurg 2008 Nov; 110 (9): 951-7
96. Weber MS, Hohlfeld R, Zamvil SS. Mechanism of action of glatiramer acetate in treatment of multiple sclerosis. Neurotherapeutics 2007 Oct; 4 (4): 647-53 (Pubitemid 47499292)
97. Iarlori C, Gambi D, Lugaresi A, et al. Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone). Mult Scler 2008 Jul; 14 (6): 739-48
98. Wolinsky JS, Narayana PA, O'Connor P, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebocontrolled trial. Ann Neurol 2007 Jan; 61 (1): 14-24 (Pubitemid 46214240)
99. Sajja BR, Narayana PA, Wolinsky JS, et al. Longitudinal magnetic resonance spectroscopic imaging of primary progressive multiple sclerosis patients treated with glatiramer acetate: multicenter study. Mult Scler 2008 Jan; 14 (1): 73-80 (Pubitemid 351541399)
100. La Mantia L, Munari LM, Lovati R. Glatiramer acetate for multiple sclerosis. Cochrane Database Syst Rev 2010; 5: CD004678
101. Gordon PH, Doorish C, Montes J, et al. Randomized controlled phase II trial of glatiramer acetate in ALS. Neurology 2006 Apr 11; 66 (7): 1117-9 (Pubitemid 44044808)
102. Meininger V, Drory VE, Leigh PN, et al. Glatiramer acetate has no impact on disease progression inALS at 40mg/day: a double-blind, randomized, multicentre, placebo-controlled trial. Amyotroph Lateral Scler 2009 Oct-Dec; 10 (5-6): 378-83
103. Laurie C, Reynolds A, Coskun O, et al. CD4+ T cells from Copolymer-1 immunized mice protect dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine model of Parkinson's disease. J Neuroimmunol 2007 Feb; 183 (1-2): 60-8 (Pubitemid 46204910)
104. Frenkel D, Maron R, Burt DS, et al. Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears beta-amyloid in a mouse model of Alzheimer disease. J Clin Invest 2005 Sep; 115 (9): 2423-33 (Pubitemid 41266204)
105. Butovsky O, Koronyo-Hamaoui M, Kunis G, et al. Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1. Proc Natl Acad Sci USA 2006 Aug 1; 103 (31): 11784-9 (Pubitemid 44182528)
106. Correale J, Villa A. The blood-brain-barrier in multiple sclerosis: functional roles and therapeutic targeting. Autoimmunity 2007 Mar; 40 (2): 148-60
107. Veldhuis WB, Derksen JW, Floris S, et al. Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat. J Cereb Blood Flow Metab 2003 Sep; 23 (9): 1029-39 (Pubitemid 37082428)
108. Biernacki K, Antel JP, Blain M, et al. Interferon beta promotes nerve growth factor secretion early in the course of multiple sclerosis. Arch Neurol 2005 Apr; 62 (4): 563-8 (Pubitemid 40489886)
109. Leary SM, Miller DH, Stevenson VL, et al. Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 2003 Jan 14; 60 (1): 44-51 (Pubitemid 36070642)
110. Montalban X, Sastre-Garriga J, Tintore M, et al. A singlecenter, randomized, double-blind, placebo-controlled study of interferon beta-1b on primary progressive and transitional multiple sclerosis. Mult Scler 2009 Oct; 15 (10): 1195-205
111. Rojas JI, Romano M, Ciapponi A, et al. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev 2010; (1): CD006643
112. Andersen O, Elovaara I, Farkkila M, et al. Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 2004 May; 75 (5): 706-10 (Pubitemid 38526680)
113. Cohen JA, Cutter GR, Fischer JS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002 Sep 10; 59 (5): 679-87
114. Kappos L, Polman C, Pozzilli C, et al. Final analysis of the European multicenter trial on IFNbeta-1b in secondaryprogressive MS. Neurology 2001 Dec 11; 57 (11): 1969-75 (Pubitemid 33126860)
115. Panitch H, Miller A, Paty D, et al. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology 2004 Nov 23; 63 (10): 1788-95 (Pubitemid 39532370)
116. Beghi E, Chio A, Inghilleri M, et al. A randomized controlled trial of recombinant interferon beta-1a in ALS: Italian Amyotrophic Lateral Sclerosis Study Group. Neurology 2000 Jan 25; 54 (2): 469-74 (Pubitemid 30078086)