3. , , , et al. Pharmacogenetics and pharmacogenomics in drug development and regulatory decision making: report of the first FDA-PWG-PhRMA-DruSafe Workshop. J Clin pharmacol 2003; 43:342–58.
6. , A plea for “omics” research in complex diseases such as multiple sclerosis – a change of mind is needed. J Neurol Sci 2004; 222:3–5.
7. Genetic basis of drug metabolism in man. Toxicol Appl Pharmacol 1964; 6:499–511.
8. , Pharmacogenetics. Br Med Bull 1961; 17:234–40.
9. , , , Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. Ame Rev Tuberculosis 1954; 70:266–73.
10. , , , et al. Genetic basis for clinical expression in multiple sclerosis. Brain 2002; 125:150–8.
11. , , , et al. Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis. Neurology 2001; 57:853–7.
12. , , , et al. BEST-PGx: design of a pharmacogenomic and pharmacogenetic study to identify criteria for prediction of treatment response to interferon-b-1b. Mult Scler 2005; 11: S245, abstract P592.
13. , , , et al. Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Hum Mol Genet 2009; 18:2078–90.
14. , DNA, drugs and chariots: on a decade of pharmacogenomics at the US FDA. Pharmacogenomics 2010; 11:507–12.
15. , Multiple sclerosis genetics–is the glass half full, or half empty? Nat Rev Neurol 2010; 6:429–37.
16. , , , , , Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat Immunol 2007; 8:74–83.
17. , et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science NY 2001; 294:1731–5.
18. , , , et al Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002; 8:500–8.
19. , , , Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: a longitudinal study in multiple sclerosis patients. Mult Scler 2009; 15:721–7.
20. , , , et al. Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1. Mult Scler 2006; 12:47–57.
21. , , , et al. Neutralizing antibodies, MxA expression and MMP-9/TIMP-1 ratio as markers of bioavailability of interferon-beta treatment in multiple sclerosis patients: a two-year follow-up study. Eur J Neurol 2010; 17:470–8.
22. , , , et al. Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event. Proc Natl Acad Sci USA 2008; 105:11839–44.
23. , , The emerging role of microRNAs in multiple sclerosis. Nat Rev Neurol 2011; 7:56–9.
24. , , , et al. Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 2007; 449:919–22.
25. , , Predicting responders to therapies for multiple sclerosis. Nat Rev Neurol 2009; 5:553–60.
26. , Multiple sclerosis pharmacogenomics: maximizing efficacy of therapy. Neurology 2010; 74 (Suppl 1):S62–9.
27. , , Pharmacogenomics of multiple sclerosis: in search for a personalized therapy. Expert Opin Pharmacother 2008; 9:3053–67.
28. , , , et al. HLA-DRB1*1501 and response to copolymer-1 therapy in relapsing-remitting multiple sclerosis. Neurology 2001; 57:1976–9.
29. , , , , et al. The HLA locus and multiple sclerosis in Spain. Role in disease susceptibility, clinical course and response to interferon-beta. J Neuroimmunol 2002; 130:194–201.
30. , , , et al. HLA class I and II alleles and response to treatment with interferon-beta in relapsing–remitting multiple sclerosis. J Neuroimmunol 2009; 210:116–9.
31. , , , et al. Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis. Genes Immun 2003; 4:147–52.
32. , , , et al. IFNAR1 and IFNAR2 polymorphisms confer susceptibility to multiple sclerosis but not to interferon-beta treatment response. J Neuroimmunol 2005; 163:165–71.
33. , , , et al. Pharmacogenomics of responsiveness to interferon IFN-beta treatment in multiple sclerosis: a genetic screen of 100 type I interferon-inducible genes. Clin Pharmacol Ther 2005; 78:635–46.
34. , , , et al. Genome-wide scan of 500,000 single-nucleotide polymorphisms among responders and nonresponders to interferon beta therapy in multiple sclerosis. Arch Neurol 2009; 66:972–8.
35. , , , et al. Genome-wide pharmacogenomic analysis of the response to interferon beta therapy in multiple sclerosis. Arch Neurol 2008; 65:337–44.
36. , , , et al. An IFNG polymorphism is associated with interferon-beta response in Spanish MS patients. J Neuroimmunol 2006; 173:196–9.
37. , , , , Pharmacogenetics of MXA SNPs in interferon-beta treated multiple sclerosis patients. J Neuroimmunol 2007; 182:6–239.
38. , , , et al. IL-10 promoter haplotype influence on interferon treatment response in multiple sclerosis. Eur J Neurol 2005; 12:171–5.
39. , , , et al. Glypican 5 is an interferon-beta response gene: a replication study. Mult Scler 2009; 15:913–917.
40. , , , et al. Replication of top markers of a genome-wide association study in multiple sclerosis in Spain. Genes Immun 2011; 12(2):100–5.
41. , , , et al. CD46 in a Spanish cohort of multiple sclerosis patients: genetics, mRNA expression and response to interferon-beta treatment. Mult Scler 2010.
42. , , , et al. Genetic polymorphisms, their allele combinations and IFN-beta treatment response in Irish multiple sclerosis patients. Pharmacogenomics 2009; 10:1177–86.
43. , , , , , et al. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers. Pharmacogenet Genom 2007; 17:657–66.
44. , , , et al. Complex immunomodulatory effects of interferon-beta in multiple sclerosis include the upregulation of T helper 1-associated marker genes. Ann Neurol 2001; 50:349–57.
45. , , , et al. Genomic effects of IFN-beta in multiple sclerosis patients. J Immunol 2003; 171:2694–702.
46. , , , et al. Microarray analysis identifies interferon beta-regulated genes in multiple sclerosis. J Neuroimmunol 2003; 139:109–18.
47. , , , , Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis. J Neuroimmunol 2004; 152:126–39.
48. , , , , , Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells. J Neuroimmunol 2004; 150:163–77.
49. , , , et al. Genome-wide network analysis reveals the global properties of IFN-beta immediate transcriptional effects in humans. J Immunol 2007; 178:5076–85.
50. , , , et al. Enhancement of chemokine expression by interferon beta therapy in patients with multiple sclerosis. Arch Neurol 2009; 66:1216–23.
51. , , , et al. Time course transcriptomics of IFNB1b drug therapy in multiple sclerosis. Autoimmunity 2010; 43:172–8.
52. , , , et al. Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS. Pharmacogenomics 2010; 11:147–61.
53. , , , et al. Network analysis of transcriptional regulation in response to intramuscular interferon-beta-1a multiple sclerosis treatment. Pharmacogenom J 2010 Oct 19 [Epub ahead of print].
54. , , , et al. Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. Brain 2003; 126:19–1429.
55. , , , et al. Genomic effects of once-weekly, intramuscular interferon-beta1a treatment after the first dose and on chronic dosing: Relationships to 5-year clinical outcomes in multiple sclerosis patients. J Neuroimmunol 2008; 205:113–25.
56. , , , et al. Transcription-based prediction of response to IFNbeta using supervised computational methods. PLoS Biol 2005; 3:e2.
57. , , , et al. Pharmacogenomics of interferon-beta therapy in multiple sclerosis: baseline IFN signature determines pharmacological differences between patients. PloS one 2008; 3:e1927.
58. , , , et al. A type I interferon signature in monocytes is associated with poor response to interferon-beta in multiple sclerosis. Brain 2009; 132:3353–65.
59. , , , , , Clinical response to glatiramer acetate correlates with modulation of IFN-gamma and IL-4 expression in multiple sclerosis. Mult Scler 2007; 13:754–62.
60. , , , , Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients. J Neuroimmunol 2008; 194:153–64.
61. , Current approaches to the identification and management of breakthrough disease in patients with multiple sclerosis. Lancet Neurol 2009; 8:545–59.
62. , Single-nucleotide polymorphisms in response to interferon-beta therapy in multiple sclerosis. J Interferon Cytokine Res 2010; 30:727–32.
63. , , , et al. Inhibitory role for GABA in autoimmune inflammation. Proc Natl Acad Sci USA 2010; 107:2580–5.
64. , , , and NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 2005; 438:1162–6.
65. , , , Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat Med 2000; 6:62–6.
66. , , , et al. Association to the Glypican-5 gene in multiple sclerosis. J Neuroimmunol 2010; 226:194–7.
67. , , , , Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action. Lancet Neurol 2005; 4:567–75.
68. , , , , Disease gene discovery through integrative genomics. Ann Rev Genomi Hum Genet 2005; 6:381–406.
69. , , , , 2005. Immune response to immunotherapy: the role of neutralising antibodies to interferon beta in the treatment of multiple sclerosis. Lancet Neurol 2005; 4:403–12.
70. , , and Absence of MxA induction by interferon beta in patients with MS reflects complete loss of bioactivity. Neurology 2009; 73:372–77.
71. , , , et al. TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta treatment in multiple sclerosis. Lancet 2003; 361:2036–43.
72. , , , et al. Neutralizing antibodies against IFN-beta in multiple sclerosis: antagonization of IFN-beta mediated suppression of MMPs. Brain 2004; 127:259–68.
73. , , , et al. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis. Lancet Neurol 2010; 9:740–50.
74. , , , , Matrix metalloproteinases and their tissue inhibitors as markers of disease subtype and response to interferon-beta therapy in relapsing and secondary-progressive multiple sclerosis patients. Ann Neurol 2001; 50:443–51.
75. , , and Molecular profiling of glatiramer acetate early treatment effects in multiple sclerosis. Dis Markers 2009; 27:63–73.
76. , , , et al. Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis. Neurology 1999; 53:1397–401.
77. , , , et al. Identification of antibodies as biological markers in serum from multiple sclerosis patients by immunoproteomic approach. J Neuroimmunol 2011; 233(1–2):175–80.
78. , , , , , Protein expression profiles in pediatric multiple sclerosis: potential biomarkers. Mult Scler 2009; 15:455–64.
79. , , , et al. IFNbeta lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS. Neurology 2003; 60:52–7.
80. , , , et al. Alterations in serum MMP-8, MMP-9, IL-12p40 and IL-23 in multiple sclerosis patients treated with interferon-beta1b. Mult Scler 2010; 16:801–9.
81. , , , et al. Changes in matrix metalloproteinases and their inhibitors during interferon-beta treatment in multiple sclerosis. Clin Immunol 2009; 130:145–50.
82. , , Identification of short-term pharmacodynamic effects of interferon-beta-1a in multiple sclerosis subjects with broad- based phenotypic profiling. J Neuroimmunol 2007; 188:103–16.
83. , , PBMCs protein expression profile in relapsing IFN-treated multiple sclerosis: A pilot study on relation to clinical findings and brain atrophy. J. Neuroimmunol 2009; 210:80–6.
84. , , Molecular network of the comprehensive multiple sclerosis brain-lesion proteome. Mult Scler 2009; 15:531–41.
85. , , , et al. Naturally presented peptides on major histocompatibility complex I and II molecules eluted from central nervous system of multiple sclerosis patients. Mol Cell Proteomics 2009; 8:2090–101.
86. , , , et al. A proteome map of axoglial specializations isolated and purified from human central nervous system. Glia 2010; 58:1949–60.
87. , , , et al. Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature 2008; 451:1076–81.
88. , , , , and Proteomic analysis of cerebrospinal fluid from multiple sclerosis patients. Proteomics 2004; 4:2117–24.
89. , , , et al. Proteomic analysis of multiple sclerosis cerebrospinal fluid. Mult Scler 2004; 10:245–60.
90. , , , et al. Lumbar cerebrospinal fluid proteome in multiple sclerosis: characterization by ultrafiltration, liquid chromatography, and mass spectrometry. J Proteome Res 2006; 5:1647–57.
91. , , , et al. Cerebrospinal fluid proteome profile in multiple sclerosis. Mult Scler 2007; 13:840–9.
92. , , , , , Quantitative proteomic analysis of the cerebrospinal fluid of patients with multiple sclerosis. J Cell Mol Med 2009; 13:1586–603.
93. , , , et al. Differential cerebro spinal fluid proteome investigation of Leber hereditary optic neuropathy (LHON) and multiple sclerosis. J Neuroimmunol 2008; 193:156–60.
94. , , , et al. CSF proteome analysis in multiple sclerosis patients by two-dimensional electrophoresis. Eur J Neurol 2008; 15:998–1001.
95. , , , et al. Multiple sclerosis-related proteins identified in cerebrospinal fluid by advanced mass spectrometry. Proteomics 2008; 8:1576–85.
96. , , , et al. CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers for conversion to definite multiple sclerosis. Neurosci Lett 2009; 452:214–7.
97. , , , et al. Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis. PloS one 2008; 3:e2559.
98. , , , et al. Proteome analysis of biomarkers in the cerebrospinal fluid of neuromyelitis optica patients. Molec Vision 2009; 15:1638–48.
99. , , , et al. Cerebrospinal fluid chitinase 3-like 1 levels are associated with conversion to multiple sclerosis. Brain 2010; 133:1082–93.
100. , , , et al. Proteomics comparison of cerebrospinal fluid of relapsing remitting and primary progressive multiple sclerosis. PloS one 2010; 5:e12442.
101. , , , et al. Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers. J Proteomics 2010; 73:1117–32.
102. , , , , , 1H-NMR spectroscopy combined with pattern recognition analysis reveals characteristic chemical patterns in urines of MS patients and non-human primates with MS-like disease. J Neurol Sci 2003; 212:21–30.
103. , , , , , Urinary neopterin and nitric oxide metabolites as markers of interferon beta-1a activity in primary progressive multiple sclerosis. Mult Scler 2010; 16:1066–72.
104. , , , Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis. Mult Scler 2008; 14:59–66.
105. , , , et al. NMR-based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases–a diagnostic tool? NMR Biomed 2010; 23:123–32.
106. , , , et al. Vitamin D metabolites are associated with clinical and MRI outcomes in multiple sclerosis patients. J Neurol Neurosurg Psychiatry 2011; 82:189–95.
107. , , , et al. Multiple sclerosis as a generalized CNS disease–comparative microarray analysis of normal appearing white matter and lesions in secondary progressive MS. J Neuroimmunol 2004; 152:154–67.
108. , , , , Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis. Ann Neurol 1996; 40:846–52.
109. , , , et al. Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann Neurol 1996; 40:853–63.
110. , , , et al. Study of cytokine induced neuropathology by high resolution proton NMR spectroscopy of rat urine. FEBS Lett 2004; 568:49–54.