Progressive MS: From pathophysiology to drug discovery

Multiple Sclerosis

Volumn 21, Issue 11, 2015, Pages 1376-1384

  Salvetti, Marco ^a   Landsman, Douglas ^b   Schwarz Lam, Peter ^c   Comi, Giancarlo ^d   Thompson, Alan J ^e   Fox, Robert J ^f  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b National Multiple Sclerosis Society   (United States)

^c ALS Society of Canada   (Canada)

^d SAN RAFFAELE HOSPITAL   (Italy)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

^f CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE   (United States)

Author keywords

academic industry collaborations; Multiple sclerosis; progressive multiple sclerosis; research agenda; therapy

Indexed keywords

ADENOSINE TRIPHOSPHATE; BENZATROPINE; BRAIN DERIVED NEUROTROPHIC FACTOR; CHEMOKINE RECEPTOR CX3CR1; CUPRIZONE; FINGOLIMOD; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 35; INTERLEUKIN 6; LACTOSYLCERAMIDE; LAQUINIMOD; LEUCINE RICH REPEAT NEURONAL PROTEIN 1; LYMPHOTOXIN; MITOCHONDRIAL DNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MUSCARINIC M1 RECEPTOR; MUSCARINIC M3 RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; OCRELIZUMAB; PROTEIN P75; PROTEIN SERINE THREONINE KINASE; STRESS ACTIVATED PROTEIN KINASE; TERIFLUNOMIDE; TRANSFORMING GROWTH FACTOR BETA ACTIVATED KINASE 1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN; VERY LATE ACTIVATION ANTIGEN 2; VASCULOTROPIN RECEPTOR;

ALZHEIMER DISEASE; ASTROCYTE; ASTROCYTOSIS; B LYMPHOCYTE; CELL SURVIVAL; CONFERENCE PAPER; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DISEASE COURSE; DNA MODIFICATION; DRUG ANTAGONISM; DRUG EFFICACY; DRUG INDUSTRY; DRUG SAFETY; DRUG SCREENING; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME INHIBITION; EPSTEIN BARR VIRUS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FOLLOW UP; GENETIC ASSOCIATION; GLIA CELL; GRAY MATTER; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOGENETICS; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; MICROGLIA; MITOCHONDRION; MULTIPLE SCLEROSIS; NERVE CELL PLASTICITY; NERVE DEGENERATION; NEUROBIOLOGY; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIGODENDROGLIA; PATHOPHYSIOLOGY; PHAGOCYTOSIS; PLURIPOTENT STEM CELL; PROTEIN EXPRESSION; STEM CELL; T LYMPHOCYTE; VIRUS REACTIVATION; DRUG DEVELOPMENT; MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE; ALLERGIC ENCEPHALOMYELITIS; IMMUNE RESPONSE; NERVOUS SYSTEM INFLAMMATION; RESEARCH; REVIEW;

DRUG DISCOVERY; HUMANS; MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE;

EID: 84985902334     PISSN: 13524585     EISSN: 14770970     Source Type: Journal    
DOI: 10.1177/1352458515603802     Document Type: Conference Paper

References (60)

1. Coetzee T, Zaratin P, Gleason TL,. Overcoming barriers in progressive multiple sclerosis research. Lancet Neurol 2015; 14: 132-133.
2. Thompson AJ,. A much-needed focus on progression in multiple sclerosis. Lancet Neurol 2015; 14: 133-135.
3. Fox RJ, Thompson AJ, Baker D, et al. Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS. Mult Scler 2012; 18: 1534-1540.
4. Magliozzi R, Howell O, Vora A, et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associated with early onset of disease and severe cortical pathology. Brain 2007; 130: 1089-1104.
5. Bar-Or A, Fawaz L, Fan B, et al. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 2010; 67: 452-461.
6. Barr TA, Shen P, Brown S, et al. B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J Exp Med 2012; 209: 1001-1010.
7. Yoshizaki A, Miyagaki T, DiLillo DJ, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 2012; 491: 264-268.
8. Shen P, Roch T, Lampropoulou V, et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 2014; 507: 366-370.
9. Guseo A, Jellinger K,. The significance of perivascular infiltrations in multiple sclerosis. J Neurol 1975; 211: 51-60.
10. Chard DT, Griffin CM, Rashid W,. Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis. Mult Scler 2004; 10: 387-391.
11. Kutzelnigg A, Lucchinetti CF, Stadelman C, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005; 128: 2705-2712.
12. Fisher E, Lee JC, Najamura K, et al. Gray matter atrophy in multiple sclerosis: A longitudinal study. Ann Neurol 2008; 64: 255-265.
13. Calabrese M, Filippi M, Gallo P,. Cortical lesions in multiple sclerosis. Nat Rev Neurol 2010; 6: 438-444.
14. Filippi M, van der Heuvel MP, Fornito A, et al. Gray matter damage predicts the accumulation of disability 13 years later in MS. Neurology 2013; 81: 1759-1767.
15. Mainero C, Louapre C,. Meningeal inflammation in multiple sclerosis: The key to the origin of cortical lesions ? Neurology 2015; 85: 12-13.
16. Gardner C, Magliozzi R, Durrenberger PF, et al. Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats. Brain 2013; 136: 3596-3608.
17. Serafini B, Rosicarelli B, Franciotta D, et al. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J Exp Med 2007; 204: 2899-2912.
18. Jaquiéry E, Jilek S, Schluep M, et al. Intrathecal immune responses to EBV in early MS. Eur J Immunol 2010; 40: 878-887.
19. Angelini DF, Serafini B, Piras E, et al. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis. PLoS Pathog 2013; 9: e1003220.
20. Lossius A, Johansen JN, Vartdal F, et al. High-throughput sequencing of TCR repertoires in multiple sclerosis reveals intrathecal enrichment of EBV-reactive CD8+ T cells. Eur J Immunol 2014; 44: 3439-3452.
21. van Nierop GP, Mautner J, Mitterreiter JG, et al. Intrathecal CD8 T-cells of multiple sclerosis patients recognize lytic Epstein-Barr virus proteins. Mult Scler. Epub ahead of print 3 2015. pii: 1352458515588581.
22. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature 2015; 532: 337-341.
23. Aspelund A, Antila S, Proulx ST, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 2015; 212: 991-999.
24. Prinz M, Priller J,. Microglia and brain macrophages in the molecular age: From origin to neuropsychiatric disease. Nat Rev Neurosci 2014; 15: 300-312.
25. Goldmann T, Wieghofer P, Müller PF, et al. A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat Neurosci 2013; 16: 1618-1626.
26. Yeung MS, Zdunek S, Bergmann O, et al. Dynamics of oligodendrocyte generation and myelination in the human brain. Cell 2014; 159: 766-774.
27. Gallo V, Deneen B,. Glial development: The crossroads of regeneration and repair in the CNS. Neuron 2014; 83: 283-308.
28. Mayo L, Trauger SA, Blain M, et al. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat Med 2014; 20: 1147-1156.
29. Brosnan CF, Raine CS,. The astrocyte in multiple sclerosis revisited. Glia 2013; 61: 453-465.
30. Junker A, Krumbholz M, Eisele S, et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 2009; 132: 3342-3352.
31. Aggarwal S, Yurlova L, Simons M,. Central nervous system myelin: Structure, synthesis and assembly. Trends Cell Biol 2011; 21: 585-593.
32. Wheeler D, Bandaru VV, Calabresi PA, et al. A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in multiple sclerosis. Brain 2008; 131: 3092-3102.
33. Wheeler D, Knapp E, Bandaru VV, et al. Tumor necrosis factor-alpha-induced neural sphingomyelinase-2 modulates synaptic plasticity by controlling the membrane insertion of NMDA receptors. J Neurochem 2009; 109: 1237-1249.
34. Kaul M,. HIVs double strike at the brain: Neuronal toxicity and compromised neurogenesis. Front Biosci 2008; 13: 2484-2494.
35. Mahad DH, Trapp BD, Lassmann H,. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015; 14: 183-193.
36. Campbell GR, Ziabreva I, Reeve AK, et al. Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann Neurol 2011; 69: 481-492.
37. Stys PK, Zamponi GW, van Minnen J, et al. Will the real multiple sclerosis please stand up? Nat Rev Neurosci 2012; 13: 507-514.
38. Stys PK,. Pathoetiology of multiple sclerosis: Are we barking up the wrong tree? F1000Prime Rep 2013; 5: 20.
39. Di Pardo A, Amico E, Favellato M, et al. FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular and mouse models of Huntington disease. Hum Mol Genet 2014; 23: 2251-2265.
40. Deogracias R, Yazdani M, Dekkers MP, et al. Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proc Natl Acad Sci U S A 2012; 109: 14230-14235.
41. Doi Y, Tacheuchi H, Horiuchi H, et al. Fingolimod phosphate attenuates oligomeric amyloid beta-induced neurotoxicity via increased brain-derived neurotrophic factor expression in neurons. PLoS One 2013; 8: e61988.
42. Fukumoto K, Mizoguchi H, Takeuchi H, et al. Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid beta-induced memory impairment. Behav Brain Res 2014; 268: 88-93.
43. Anthony DC, Sibson NR, Losey P, et al. Investigation of immune and CNS-mediate effects of fingolimod in the focal delayed-type hypersensitivity multiple sclerosis model. Neuropharmacology 2014; 79: 534-541.
44. Brück W, Pförtner R, Pham T, et al. Reduced astrocytic NF-kB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol 2012; 124: 411-424.
45. Hawker K, OConnor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized, double-blind placebo-controlled multicenter trial. Ann Neurol 2009; 66: 460-471.
46. Mi S, Pepinski RB, Cadavid D,. Blocking LINGO-1 as a therapy to promote CNS repair: From concept to the clinic. CNS Drugs 2013; 27: 493-503.
47. Bennet DA, De Jager PL,. Building a pipeline to discover and validate novel therapeutic targets and lead compounds for Alzheimers disease. Biochem Pharmacol 2014; 88: 617-630.
48. Califano A, Butte AJ, Friend S, et al. Leveraging models of cell regulation and GWAS data in integrative network-based association studies. Nat Genet 2012; 44: 841-847.
49. Chen JC, Alvarez MJ, Talos F, et al. Identification of causal genetic drivers of human disease through systems-level analysis of regulatory networks. Cell 2014; 159: 402-414.
50. Aubry S, Shin W, Crary JF, et al. Assembly and interrogation of Alzheimers disease genetic networks reveal novel regulators of progression. PLoS One 2015; 10: e0120352.
51. Brichta L, Shin W, Jackson-Lewis V, et al. Satb1 orchestrates an intrinsic network against dopaminergic neuron degeneration. Nat Neurosci 2015, in press.
52. Ikiz B, Alvarez MJ, Ré DB, et al. The regulatory machinery of neurodegeneration in in vitro models of amyotrophic lateral sclerosis. Cell Rep 2015; 12: 335-345.
53. Wang L, Khankhanian P, Baranzini SE, et al. iCTNet: A Cytoscape plugin to produce and analyze integrative complex traits networks. BMC Bioinformatics 2011; 12: 380.
54. Deshmukh VA, Tardif V, Lyssiotis CA, et al. A regenerative approach to the treatment of multiple sclerosis. Nature 2013; 502: 327-332.
55. Mei F, Fancy SP, Shen YA, et al. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med 2014; 20: 954-960.
56. Najm FJ, Madhavan M, Zaremba A, et al. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature 2015; 522: 216-220.
57. Sobottka B, Ziegler U, Kaech A, et al. CNS live imaging reveals a new mechanism of myelination: The liquid croissant model. Glia 2011; 59: 1841-1849.
58. Fox IJ, Daley GQ, Goldman SA, et al. Stem cells therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease. Science 2014; 345: 1247391.
59. Laterza C, Merlini A, De Feo D, et al. iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF. Nat Commun 2013; 4: 2597.
60. Baker D, Amor S,. Mouse models of multiple sclerosis: Lost in translation? Curr Pharm Des 2015; 21: 2440-2452.