Advanced search
Publication Cover
Expert Opinion on Pharmacotherapy Volume 9, 2008 - Issue 17
Submit an article Journal homepage
187
Views
22
CrossRef citations to date
0
Altmetric
Review

Pharmacogenomics of multiple sclerosis: in search for a personalized therapy

Iván Martinez-Forero University of Navarra, Center for Applied Medical Research (CIMA), Department of Neuroscience, Neuroimmunology Lab 2.05, 31008 Pamplona, Spain + 34 948 194 700; +34 948 194 715;[email protected]; University of Navarra, Department of Physics and Applied Mathematics, Spain
, MD,
Antonio Pelaez University of Navarra, Department of Physics and Applied Mathematics, Spain
, PhD &
Pablo Villoslada University of Navarra, Center for Applied Medical Research (CIMA), Department of Neuroscience, Neuroimmunology Lab 2.05, 31008 Pamplona, Spain + 34 948 194 700; +34 948 194 715;[email protected]
, MD
Pages 3053-3067 | Published online: 12 Nov 2008

Bibliography

  • Hauser SL, Oksenberg JR. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 2006;52(1):61-76
  • Miller D. Multiple sclerosis: new insights and therapeutic progress. Lancet Neurol 2007;6(1):5-6
  • Greenberg BM, Calabresi PA. Future research directions in multiple sclerosis therapies. Semin Neurol 2008;28(1):121-7
  • Orton SM, Herrera BM, Yee IM, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. Lancet Neurol 2006;5(11):932-6
  • Villoslada P, Oksenberg JR, Rio J, Montalban X. Clinical characteristics of responders to interferon therapy for relapsing MS. Neurology 2004;62(9):1653
  • Waubant E, Vukusic S, Gignoux L, et al. Clinical characteristics of responders to interferon therapy for relapsing MS. Neurology 2003;61(2):184-9
  • Trusheim MR, Berndt ER, Douglas FL. Stratified medicine: strategic and economic implications of combining drugs and clinical biomarkers. Nat Rev Drug Discov 2007;6(4):287-93
  • Bielekova B, Martin R. Development of biomarkers in multiple sclerosis. Brain 2004;127(Pt 7):1463-78
  • Danna EA, Nolan GP. Transcending the biomarker mindset: deciphering disease mechanisms at the single cell level. Curr Opin Chem Biol 2006;10(1):20-7
  • Miller DH. Biomarkers and surrogate outcomes in neurodegenerative disease: lessons from multiple sclerosis. NeuroRx 2004;1(2):284-94
  • Gudiksen M, Fleming E, Furstenthal L, Ma P. What drives success for specialty pharmaceuticals? Nat Rev Drug Discov 2008;7(7):563-7
  • Trojano M, Pellegrini F, Fuiani A, et al. New natural history of interferon-beta-treated relapsing multiple sclerosis. Ann Neurol 2007;61(4):300-6
  • Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 2005;5(5):375-86
  • He XS, Ji X, Hale MB, et al. Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race. Hepatology 2006;44(2):352-9
  • Goldstein DB, Tate SK, Sisodiya SM. Pharmacogenetics goes genomic. Nat Rev Genet 2003;4(12):937-47
  • Axtell RC, Steinman L. Type 1 interferons cool the inflamed brain. Immunity 2008;28(5):600-2
  • Benveniste EN, Qin H. Type I interferons as anti-inflammatory mediators. Sci STKE 2007;2007(416):e70
  • Waubant E, Goodkin D, Bostrom A, et al. IFNbeta lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS. Neurology 2003;60(1):52-7
  • Prinz M, Schmidt H, Mildner A, et al. Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 2008;28(5):675-86
  • Guo B, Chang EY, Cheng G. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J Clin Invest 2008;118(5):1680-90
  • Cunningham S, Graham C, Hutchinson M, 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(6):635-46
  • Villoslada P, Barcellos LF, Rio J, 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(1-2):194-201
  • Sriram U, Barcellos LF, Villoslada P, et al. Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis. Genes Immun 2003;4(2):147-52
  • Byun E, Caillier SJ, Montalban X, et al. Genome-wide pharmacogenomic analysis of the response to interferon beta therapy in multiple sclerosis. Arch Neurol 2008;65(3):337-44
  • Wandinger KP, Lunemann JD, Wengert O, et al. TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta treatment in multiple sclerosis. Lancet 2003;361(9374):2036-43
  • Petzold A, Brassat D, Mas P, et al. Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis. Mult Scler 2004;10(3):281-3
  • Fernandez O, Fernandez V, Mayorga C, et al. HLA class II and response to interferon-beta in multiple sclerosis. Acta Neurol Scand 2005;112(6):391-4
  • Leyva L, Fernandez O, Fedetz M, et al. IFNAR1 and IFNAR2 polymorphisms confer susceptibility to multiple sclerosis but not to interferon-beta treatment response. J Neuroimmunol 2005;163(1-2):165-71
  • Weinstock-Guttman B, Tamano-Blanco M, Bhasi K, et al. Pharmacogenetics of MXA SNPs in interferon-beta treated multiple sclerosis patients. J Neuroimmunol 2007;182(1-2):236-9
  • Rio J, Nos C, Tintore M, et al. Defining the response to interferon-beta in relapsing–remitting multiple sclerosis patients. Ann Neurol 2006;59(2):344-52
  • Rudick RA, Lee JC, Simon J, et al. Defining interferon beta response status in multiple sclerosis patients. Ann Neurol 2004;56(4):548-55
  • Sturzebecher S, Wandinger KP, Rosenwald A, et al. Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. Brain 2003;126(Pt 6):1419-29
  • Katsoulidis E, Li Y, Mears H, Platanias LC. The p38 mitogen-activated protein kinase pathway in interferon signal transduction. J Interferon Cytokine Res 2005;25(12):749-56
  • Kaur S, Uddin S, Platanias LC. The PI3′ kinase pathway in interferon signaling. J Interferon Cytokine Res 2005;25(12):780-7
  • Mogensen KE, Lewerenz M, Reboul J, et al. The type I interferon receptor: structure, function, and evolution of a family business. J Interferon Cytokine Res 1999;19(10):1069-98
  • Pfeffer LM, Basu L, Pfeffer SR, et al. The short form of the interferon alpha/beta receptor chain 2 acts as a dominant negative for type I interferon action. J Biol Chem 1997;272(17):11002-5
  • Domanski P, Witte M, Kellum M, et al. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J Biol Chem 1995;270(37):21606-11
  • Darnell JE Jr, Kerr IM, Stark GR. Jak–STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994;264(5164):1415-21
  • Baranzini SE, Mousavi P, Rio J, et al. Transcription-based prediction of response to IFNbeta using supervised computational methods. PLoS Biol 2005;3(1):e2
  • Reich NC, Liu L. Tracking STAT nuclear traffic. Nat Rev Immunol 2006;6(8):602-12
  • Weinstock-Guttman B, Badgett D, Patrick K, et al. Genomic effects of IFN-beta in multiple sclerosis patients. J Immunol 2003;171(5):2694-702
  • Feng X, Petraglia AL, Chen M, et al. Low expression of interferon-stimulated genes in active multiple sclerosis is linked to subnormal phosphorylation of STAT1. J Neuroimmunol 2002;129(1-2):205-15
  • Uddin S, Sassano A, Deb DK, et al. Protein kinase C-delta (PKC-delta ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. J Biol Chem 2002;277(17):14408-16
  • Lekmine F, Uddin S, Sassano A, et al. Activation of the p70 S6 kinase and phosphorylation of the 4E-BP1 repressor of mRNA translation by type I interferons. J Biol Chem 2003;278(30):27772-80
  • Fujimoto M, Naka T. Regulation of cytokine signaling by SOCS family molecules. Trends Immunol 2003;24(12):659-66
  • Liu B, Liao J, Rao X, et al. Inhibition of Stat1-mediated gene activation by PIAS1. Proc Natl Acad Sci USA 1998;95(18):10626-31
  • Gniadek P, Aktas O, Wandinger KP, et al. Systemic IFN-beta treatment induces apoptosis of peripheral immune cells in MS patients. J Neuroimmunol 2003;137(1-2):187-96
  • Sharief MK, Noori MA, Zoukos Y. Reduced expression of the inhibitor of apoptosis proteins in T cells from patients with multiple sclerosis following interferon-beta therapy. J Neuroimmunol 2002;129(1-2):224-31
  • Sharief MK, Semra YK. Down-regulation of survivin expression in T lymphocytes after interferon beta-1a treatment in patients with multiple sclerosis. Arch Neurol 2002;59(7):1115-21
  • Fernald GH, Knott S, Pachner A, et al. Genome-wide network analysis reveals the global properties of IFN-beta immediate transcriptional effects in humans. J Immunol 2007;178(8):5076-85
  • Hong J, Zang YC, Hutton G, et al. Gene expression profiling of relevant biomarkers for treatment evaluation in multiple sclerosis. J Neuroimmunol 2004;152(1-2):126-39
  • Malucchi S, Gilli F, Caldano M, et al. Predictive markers for response to interferon therapy in patients with multiple sclerosis. Neurology 2008;70(13 Pt 2):1119-27
  • Millonig A, Dressel A, Bahner D, et al. MxA protein–an interferon beta biomarker in primary progressive multiple sclerosis patients. Eur J Neurol 2008;15(8):822-6
  • Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997;337(3):141-7
  • Koike F, Satoh J, Miyake S, et al. Microarray analysis identifies interferon beta-regulated genes in multiple sclerosis. J Neuroimmunol 2003;139(1-2):109-18
  • Huang YM, Adikari S, Bave U, et al. Multiple sclerosis: interferon-beta induces CD123(+)BDCA2- dendritic cells that produce IL-6 and IL-10 and have no enhanced type I interferon production. J Neuroimmunol 2005;158(1-2):204-12
  • Nicoletti F, Di Marco R, Patti F, et al. Short-term treatment of relapsing remitting multiple sclerosis patients with interferon (IFN)-beta1B transiently increases the blood levels of interleukin (IL)-6, IL-10 and IFN-gamma without significantly modifying those of IL-1beta, IL-2, IL-4 and tumour necrosis factor-alpha. Cytokine 2000;12(6):682-7
  • Espejo C, Brieva L, Ruggiero G, et al. IFN-beta treatment modulates the CD28/CTLA-4-mediated pathway for IL-2 production in patients with relapsing–remitting multiple sclerosis. Mult Scler 2004;10(6):630-5
  • Schreiner B, Mitsdoerffer M, Kieseier BC, et al. Interferon-beta enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis. J Neuroimmunol 2004;155(1-2):172-82
  • Jensen J, Krakauer M, Sellebjerg F. Cytokines and adhesion molecules in multiple sclerosis patients treated with interferon-beta1b. Cytokine 2005;29(1):24-30
  • O'Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol 2007;7(6):425-8
  • Martinez-Forero I, Garcia-Munoz R, Martinez-Pasamar S, et al. IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. Eur J Immunol 2008;38(2):576-86
  • Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 2008;8(6):458-66
  • Laver T, Nozell SE, Benveniste EN. IFN-beta-mediated inhibition of IL-8 expression requires the ISGF3 components Stat1, Stat2, and IRF-9. J Interferon Cytokine Res 2008;28(1):13-23
  • Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol 2005;23:683-747
  • Bugeon L, Dallman MJ. Costimulation of T cells. Am J Respir Crit Care Med 2000;162(4 Pt 2):S164-8
  • Liu Z, Pelfrey CM, Cotleur A, et al. Immunomodulatory effects of interferon beta-1a in multiple sclerosis. J Neuroimmunol 2001;112(1-2):153-62
  • Marckmann S, Wiesemann E, Hilse R, et al. Interferon-beta up-regulates the expression of co-stimulatory molecules CD80, CD86 and CD40 on monocytes: significance for treatment of multiple sclerosis. Clin Exp Immunol 2004;138(3):499-506
  • Shapiro S, Galboiz Y, Lahat N, et al. The ‘immunological-synapse’ at its APC side in relapsing and secondary-progressive multiple sclerosis: modulation by interferon-beta. J Neuroimmunol 2003;144(1-2):116-24
  • Iglesias AH, Camelo S, Hwang D, et al. Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells. J Neuroimmunol 2004;150(1-2):163-77
  • Wiesemann E, Deb M, Trebst C, et al. Effects of interferon-beta on co-signaling molecules: upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon-beta treatment in patients with multiple sclerosis. Mult Scler 2008;14(2):166-76
  • Rudd CE. The reverse stop-signal model for CTLA4 function. Nat Rev Immunol 2008;8(2):153-60
  • Bruce SP, Boyce EG. Update on abatacept: a selective costimulation modulator for rheumatoid arthritis. Ann Pharmacother 2007;41(7):1153-62
  • Suppiah V, Alloza I, Heggarty S, et al. The CTLA4+49 A/G*G-CT60*G haplotype is associated with susceptibility to multiple sclerosis in Flanders. J Neuroimmunol 2005;164(1-2):148-53
  • Ligers A, Xu C, Saarinen S, et al. The CTLA-4 gene is associated with multiple sclerosis. J Neuroimmunol 1999;97(1-2):182-90
  • Harbo HF, Celius EG, Vartdal F, Spurkland A. CTLA4 promoter and exon 1 dimorphisms in multiple sclerosis. Tissue Antigens 1999;53(1):106-10
  • Alizadeh M, Babron MC, Birebent B, et al. Genetic interaction of CTLA-4 with HLA-DR15 in multiple sclerosis patients. Ann Neurol 2003;54(1):119-22
  • Malferrari G, Stella A, Monferini E, et al. Ctla4 and multiple sclerosis in the Italian population. Exp Mol Pathol 2005;78(1):55-7
  • Hafler DA, Compston A, Sawcer S, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007;357(9):851-62
  • Thio CL, Mosbruger TL, Kaslow RA, et al. Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection. J Virol 2004;78(20):11258-62
  • Maier LM, Anderson DE, De Jager PL, et al. Allelic variant in CTLA4 alters T cell phosphorylation patterns. Proc Natl Acad Sci USA 2007;104(47):18607-12
  • Palacios R, Comas D, Villoslada P. Genomic regulation of CTLA4 and autoimmunity. J Neuroimmunol 2008; In press
  • Bechmann I, Galea I, Perry VH. What is the blood–brain barrier (not)? Trends Immunol 2007;28(1):5-11
  • Galea I, Bechmann I, Perry VH. What is immune privilege (not)? Trends Immunol 2007;28(1):12-18
  • Yednock TA, Cannon C, Fritz LC, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992;356(6364):63-6
  • Soilu-Hanninen M, Laaksonen M, Hanninen A, et al. Downregulation of VLA-4 on T cells as a marker of long term treatment response to interferon beta-1a in MS. J Neuroimmunol 2005;167(1-2):175-82
  • Graber J, Zhan M, Ford D, et al. Interferon-beta-1a induces increases in vascular cell adhesion molecule: implications for its mode of action in multiple sclerosis. J Neuroimmunol 2005;161(1-2):169-76
  • Rice GP, Hartung HP, Calabresi PA. Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale. Neurology 2005;64(8):1336-42
  • Sheremata WA, Vollmer TL, Stone LA, et al. A safety and pharmacokinetic study of intravenous natalizumab in patients with MS. Neurology 1999;52(5):1072-4
  • Lindberg RL, Achtnichts L, Hoffmann F, et al. Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients. J Neuroimmunol 2008;194(1-2):153-64
  • Ransohoff RM. Natalizumab for multiple sclerosis. N Engl J Med 2007;356(25):2622-9
  • Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoen cephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 2005;353(4):369-74
  • Yousry TA, Major EO, Ryschkewitsch C, et al. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med 2006;354(9):924-33
  • Gold R, Jawad A, Miller DH, et al. Expert opinion: guidelines for the use of natalizumab in multiple sclerosis patients previously treated with immunomodulating therapies. J Neuroimmunol 2007;187(1-2):156-8
  • Farina C, Weber MS, Meinl E, et al. Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action. Lancet Neurol 2005;4(9):567-75
  • Allie R, Hu L, Mullen KM, et al. Bystander modulation of chemokine receptor expression on peripheral blood T lymphocytes mediated by glatiramer therapy. Arch Neurol 2005;62(6):889-94
  • Fusco C, Andreone V, Coppola G, et al. HLA-DRB1*1501 and response to copolymer-1 therapy in relapsing-remitting multiple sclerosis. Neurology 2001;57(11):1976-9
  • Grossman I, Avidan N, Singer C, et al. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers. Pharmacogenet Genomics 2007;17(8):657-66
  • Kitano H. Systems biology: a brief overview. Science 2002;295(5560):1662-4
  • Kitano H. Computational systems biology. Nature 2002;420(6912):206-10
  • Butcher EC. Can cell systems biology rescue drug discovery? Nat Rev Drug Discov 2005;4(6):461-7
  • Goni J, Esteban FJ, Velez De Mendizabal N, et al. A computational analysis of the protein–protein interaction networks in neurodegenerative diseases. BMC Syst Biol 2008;2(1):52
  • Palacios R, Goni J, Martinez-Forero I, et al. A network analysis of the human T-cell activation gene network identifies JAGGED1 as a therapeutic target for autoimmune diseases. PLoS One 2007;2(11):e1222
  • Alon U. Network motifs: theory and experimental approaches. Nat Rev Genet 2007;8(6):450-61
  • Angeli D, Ferrell JE Jr, Sontag ED. Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems. Proc Natl Acad Sci USA 2004;101(7):1822-7
  • Craciun G, Tang Y, Feinberg M. Understanding biostability in complex enzyme-driven reaction networks. Proc Natl Acad Sci USA 2006;103(23):8697-702
  • Kholodenko BN. Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 2006;7(3):165-76
  • Feinerman O, Veiga J, Dorfman JR, et al. Variability and robustness in T cell activation from regulated heterogeneity in protein levels. Science 2008;321(5892):1081-4
  • Villoslada P, Oksenberg JR. Neuroinformatics in clinical practice: are computers going to help neurological patients and their physicians? Future Neurol 2006;1(2):1-12

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.