Systems biology impact on antiepileptic drug discovery

Epilepsy Research

Volumn 98, Issue 2-3, 2012, Pages 104-115

  Margineanu, Doru Georg ^a  

^a UNIVERSITY OF MONS   (Belgium)

Author keywords

Epilepsy etiology; Hypersynchrony; Multi target drug; Network pharmacology; Poly pharmacology; Systems biology

Indexed keywords

ANTICONVULSIVE AGENT; DRUG RECEPTOR; ETIRACETAM;

ANTICONVULSANT ACTIVITY; AUDIOGENIC SEIZURE; BRAIN FUNCTION; BRAIN REGION; DRUG MECHANISM; DRUG RECEPTOR BINDING; EPILEPSY; EPILEPTIC DISCHARGE; EPILEPTOGENESIS; GENE EXPRESSION; GENE MUTATION; HISTOLOGY; HUMAN; MOLECULAR BIOLOGY; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SYSTEMS BIOLOGY; TEMPORAL LOBE EPILEPSY;

ANIMALS; ANTICONVULSANTS; DRUG DISCOVERY; EPILEPSY; HUMANS; SYSTEMS BIOLOGY;

EID: 84856454917     PISSN: 09201211     EISSN: 18726844     Source Type: Journal    
DOI: 10.1016/j.eplepsyres.2011.10.006     Document Type: Review

References (107)

1. Albert R., Jeong H., Barabási A.L. Error and attack tolerance of complex networks. Nature 2000, 406:378-382.
2. 2+ transients and epileptiform potentials in hippocampal neurons. NeuroReport 2003, 14:471-475.
3. Arrowsmith J. Phase III and submission failures: 2007-2010. Nat. Rev. Drug Disc. 2011, 10:1.
4. Ban T.A. Paul Adriaan Jan Janssen, 1926-2003. Neuropsychopharmacology 2004, 29:1579-1580.
5. Barabási A.L., Oltvai Z.N. Network biology: understanding the cell's functional organization. Nat. Rev. Genet. 2004, 5:101-113.
6. Baranzini S.E. Gene expression profiling in neurological disorders. Toward a systems-level understanding of the brain. Neuro. Mol. Med. 2004, 6:31-51.
7. Barkmeier D.T., Loeb J.A. An animal model to study the clinical significance of interictal spiking. Clin. EEG Neurosci. 2009, 40:234-238.
8. Berkovic S.F., Mulley J.C., Scheffer I.E., Petrou S. Human epilepsies: interaction of genetic and acquired factors. Trends Neurosci. 2006, 29:391-397.
9. Bernasconi R., Klein M., Martin P., Christen P., Hafner T., Portet C., Schmutz M. Gamma-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. J. Neural Transm. 1988, 72:213-233.
10. Bialer M., Johannessen S.I., Levy R.H., Perucca E., Tomson T., White H.S. Progress report on new antiepileptic drugs: a summary of Tenth Eilat Conference (EILAT X). Epilepsy Res. 2010, 92:89-124.
11. Bianchi M.T., Pathmanathan J., Cash S.S. From ion channels to complex networks: magic bullet versus magic shotgun approaches to anticonvulsant pharmacotherapy. Med. Hypoth. 2009, 72:297-305.
12. Booth B., Zemmel R. Prospects for productivity. Nat. Rev. Drug Disc. 2004, 3:451-456.
13. Brodie M.J., Kwan P. Staged approach to epilepsy management. Neurology 2002, 58:S2-S8.
14. Brodie M.J., Shorvon S.D., Canger R., Halász P., Johannessen S., Thompson P., Wieser H.G., Wolf P. ILAE Commission report. Commission on European affairs: appropriate standards of epilepsy care across Europe. Epilepsia 1997, 38:1245-1250.
15. Brodie M.J., Sills G.J. Combining AEDs - rational polytherapy?. Seizure 2011, 20:369-375.
16. Butcher E.C., Berg E.L., Kunkel E.J. Systems biology in drug discovery. Nat. Biotechnol. 2004, 22:1253-1259.
17. i increase induced by ATP and bradykinin in PC12 cells. J. Pharm. Exp. Ther. 2005, 13:720-730.
18. Chateauvieux S., Morceau F., Dicato M., Diederich M. Molecular and therapeutic potential and toxicity of valproic acid. J. Biomed. Biotech. 2010, article ID 479364. 10.1155/2010/479364.
19. Cressey D. Traditional drug-discovery model ripe for reform. Nature 2011, 471:17-18.
20. Crino P.B. Gene expression, genetics, and genomics in epilepsy: some answers, more questions. Epilepsia 2007, 48(Suppl. 2):42-50.
21. Csermely P., Agoston V., Pongor S. The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol. Sci. 2005, 26:178-182.
22. de Curtis M., Avanzini G. Interictal spikes in focal epileptogenesis. Prog. Neurobiol. 2001, 63:541-567.
23. Dragunow M. The adult human brain in preclinical drug development. Nat. Rev. Drug Disc. 2008, 7:659-666.
24. Drews J. Genomic sciences and the medicines of tomorrow. Nat. Biotechnol. 1996, 14:1516-1518.
25. Faingold C.L. Emergent properties of CNS neuronal networks as targets for pharmacology: application to anticonvulsant drug action. Prog. Neurobiol. 2004, 72:55-85.
26. Frankel W.N. Detecting genes in new and old mouse models for epilepsy: a prospectus through the magnifying glass. Epilepsy Res. 1999, 36:97-110.
27. Franz S. Playing dirty. Nature 2005, 437:942-943.
28. Fredholm B., Abbott A. New targets for drug action: is high selectivity always beneficial?. Trends Pharmacol. Sci. 1990, 11:175-178.
29. French J.A., Kanner A.M., Bautista J., Abou-Khalil B., Browne T., Harden C.L., Theodore W.H., Bazil C., Stern J., Schachter S.C., Bergen D., Hirtz D., Montouris G.D., Nespeca M., Gidal B., Marks W.J., Turk W.R., Fischer J.H., Bourgeois B., Wilner A., Faught R.E., Sachdeo R.C., Beydoun A., Glauser T.A. Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy. Neurology 2004, 62:1252-1260.
30. Glasscock E., Qian J., Yoo J.W., Noebels J.L. Masking epilepsy by combining two epilepsy genes. Nat. Neurosci. 2007, 10:1554-1558.
31. Hood L., Perlmutter R.M. The impact of systems approaches on biological problems in drug discovery. Nat. Biotechnol. 2004, 22:1215-1217.
32. Hopkins A.L. Network pharmacology: network biology illuminates our understanding of drug action. Nat. Biotechnol. 2007, 24:1110-1111.
33. Hopkins A.L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol. 2008, 4:682-690.
34. Hopkins A.L. Predicting promiscuity. Nature 2009, 462:167-168.
35. Ideker T., Sharan R. Protein networks in disease. Genome Res 2008, 18:644-652.
36. In Vivo Pharmacology Training Group The fall and rise of in vivo pharmacology. Trends Pharmacol. Sci. 2002, 23:13-18.
37. Kasperavičiūte D., Catarino C.B., Heinzen E.L., Depondt C., Cavalleri G.L., Caboclo L.O., Tate S.K., Jamnadas-Khoda J., Chinthapalli K., Clayton L.M., Shianna K.V., Radtke R.A., Mikati M.A., Gallentine W.B., Husain A.M., Alhusaini S., Leppert D., Middleton L.T., Gibson R.A., Johnson M.R., Matthews P.M., Hosford D., Heuser K., Amos L., Ortega M., Zumsteg D., Wieser H.G., Steinhoff B.J., Kramer G., Hansen J., Dorn T., Kantanen A.M., Gjerstad L., Peuralinna T., Hernandez D.G., Eriksson K.J., Kalviainen R.K., Doherty C.P., Wood N.W., Pandolfo M., Duncan J.S., Sander J.W., Delanty N., Goldstein D.B., Sisodiya S.M. Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study. Brain 2010, 133:2136-2147.
38. Kaufmann S.H.E. Paul Ehrlich: founder of chemotherapy. Nat. Rev. Drug Disc. 2008, 7:373.
39. Kearney J.A., Yang Y., Beyer B., Bergren S.K., Claes L., Dejonghe P., Frankel W.N. Severe epilepsy resulting from genetic interaction between Scn2a and Kcnq2. Hum. Mol. Genet. 2006, 15:1043-1048.
40. Keiser M.J., Setola V., Irwin J.J., Laggner C., Abbas A.I., Hufeisen S.J., Jensen N.H., Kuijer M.B., Matos R.C., Tran T.B., Whaley R., Glennon R.A., Hert J., Thomas K.L., Edwards D.D., Shoichet B.K., Roth B.L. Predicting new molecular targets for known drugs. Nature 2009, 462:175-181.
41. Keith C.T., Borisy A.A., Stockwel B.R. Multicomponent therapeutics for networked systems. Nat. Rev. Drug Disc. 2005, 4:71-78.
42. Kitano H. Systems biology: a brief overview. Science 2002, 295:1662-1664.
43. Kola I., Landis J. Can the pharmaceutical industry reduce attrition rates?. Nat. Rev. Drug Disc. 2004, 3:711-716.
44. Kwan P., Brodie M.J. Refractory epilepsy: mechanisms and solutions. Exp. Rev. Neurother. 2006, 6:397-406.
45. Lauffenburger D.A. Cell signaling pathways as control modules: complexity for simplicity?. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:5031-5033.
46. Lipton S.A. Turning down, but not off. Neuroprotection requires a paradigm shift in drug development. Nature 2004, 428:473.
47. Loeb J.A. A human systems biology approach to discover new drug targets in epilepsy. Epilepsia 2010, 51(Suppl. 3):171-177.
48. Loeb J.A. Identifying targets for preventing epilepsy using systems biology. Neurosci. Lett. 2011, 497:205-212.
49. Löscher W. Valproic acid. Mechanisms of action. Antiepileptic Drugs 2002, Lippincott Williams & Wilkins, Philadelphia, pp. 767-779. 5th ed. R.H. Levy (Ed.).
50. Löscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure 2011, 20:359-368.
51. Löscher W., Brandt C. Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. Pharmacol. Rev. 2010, 62:668-700.
52. Löscher W., Schmidt D. Strategies in antiepileptic drug development: is rational drug design superior to random screening and structural variation?. Epilepsy Res. 1994, 17:95-134.
53. Löscher W., Schmidt D. New horizons in the development of antiepileptic drugs. Epilepsy Res. 2002, 50:3-16.
54. Löscher W., Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia 2011, 52:657-678.
55. Lukasiuk K., Pitkänen A. Large-scale analysis of gene expression in epilepsy research: is synthesis already possible?. Neurochem. Res. 2004, 29:1169-1178.
56. Lukyanetz E.A., Shkryl V.M., Kostyuk P.G. Selective blockade of N-type calcium channels by levetiracetam. Epilepsia 2002, 43:9-18.
57. Lynch B.A., Lambeng N., Nocka K., Kensel-Hammes P., Bajjalieh S.M., Matagne A., Fuks B. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:9861-9866.
58. Lytton W.W. Computer modelling of epilepsy. Nat. Rev. Neurosci. 2008, 9:626-637.
59. Macdonald R.L. Is there a mechanistic basis for rational polypharmacy?. Epilepsy Res. 1996, Suppl. 11:79-93.
60. Madeja M., Margineanu D.G., Gorji A., Siep E., Boerrigter P., Klitgaard H., Speckmann E.-J. Reduction of voltage-operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action?. Neuropharmacology 2003, 45:661-671.
61. Mantegazza M., Rusconi R., Scalmani P., Avanzini G., Franceschetti S. Epileptogenic ion channel mutations: from bedside to bench and, hopefully, back again. Epilepsy Res. 2010, 92:1-29.
62. Margineanu D.G. Epileptic hypersynchrony revisited. NeuroReport 2010, 21:963-967.
63. Margineanu D.G., Klitgaard H. Levetiracetam mechanisms of action. Antiepileptic Drugs 2002, Lippincott Williams & Wilkins, Philadelphia, pp. 419-427. 5th ed. R.H. Levy (Ed.).
64. Margineanu D.G., Klitgaard H. Mechanisms of drug resistance in epilepsy: relevance for antiepileptic drug discovery. Expert Opin. Drug Disc. 2009, 4:23-32.
65. Matagne A., Margineanu D.G., Kenda B., Michel P., Klitgaard H. Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein SV2A. Br. J. Pharmacol. 2008, 154:1662-1671.
66. McCormick D.A., Contreras D. On the cellular and network bases of epileptic seizures. Annu. Rev. Physiol. 2001, 63:815-846.
67. Mencher S.K., Wang L.G. Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin. Pharmacol. 2005, 5(3).
68. Morphy R., Rankovik Z. Fragments, network biology and designing multiple ligands. Drug Disc. Today 2007, 12:156-160.
69. Nearing K., Madhavan D., Devinsky O. Temporal lobe epilepsy: a progressive disorder?. Rev. Neurol. Dis. 2007, 4:122-127.
70. 2+ current in pyramidal neurones of rat hippocampal slices. Neurosci. Lett. 2001, 306:5-8.
71. Noorbakhsh F., Overall C.M., Power C. Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology. Trends Neurosci. 2009, 32:88-100.
72. O'Connor T., Wong H.Y. Emergent properties. The Stanford Encyclopedia of Philosophy 2009, Springer. http://plato.stanford.edu/archives/spr2009/entries/properties-emergent/, E.N. Zalta (Ed.).
73. Park K., Lee S., Ahn H.-S., Kim D. Predicting the multi-modal binding propensity of small molecules: towards an understanding of drug promiscuity. Mol. BioSyst. 2009, 5:844-853.
74. Paulson L., Persson Å., Vonck K., Van Dycke A., Kuhn H.G., Boon P., Ben-Menachem E., Raedt R. Effect of levetiracetam on hippocampal protein expression and cell proliferation in rats. Epilepsy Res. 2010, 90:110-120.
75. Peterson R.T. Chemical biology and the limits of reductionism. Nat. Chem. Biol. 2008, 4:635-638.
76. Pitkänen A. Therapeutic approaches to epileptogenesis - hope on the horizon. Epilepsia 2010, 51(Suppl. 3):2-17.
77. Pitkänen A., Sutula T.P. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol. 2002, 1:173-181.
78. Prigogine I. Introduction to Thermodynamics of Irreversible Processes 1955, Wiley Interscience, New York.
79. Rakhade S.N., Yao B., Ahmed S., Asano E., Beaumont T.L., Shah A.K., Draghici S., Krauss R., Chugani H.T., Sood S., Loeb J.A. A common pattern of persistent gene activation in human neocortical epileptic foci. Ann. Neurol. 2005, 58:736-747.
80. Rakhade S.N., Shah A.K., Agarwal R., Yao B., Asano E., Loeb J.A. Activity-dependent gene expression correlates with interictal spiking in human neocortical epilepsy. Epilepsia 2007, 48(Suppl. 5):86-95.
81. Reid C.A., Berkovic S.F., Petrou S. Mechanisms of human inherited epilepsies. Prog. Neurobiol. 2009, 87:41-57.
82. Rogawski M.A. Molecular targets versus models for new antiepileptic drug discovery. Epilepsy Res. 2006, 68:22-28.
83. Rogawski M.A. Brivaracetam: a rational drug discovery success story. Br. J. Pharmacol. 2008, 154:1555-1557.
84. Rogawski M.A., Löscher W. The neurobiology of antiepileptic drugs. Nat. Rev. Neurosci. 2004, 5:553-564.
85. Rosenberg G. The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees?. Cell Mol. Life Sci. 2007, 64:2090-2103.
86. Roth B.L., Sheffler D.J., Kroeze W.K. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Disc. 2004, 3:353-359.
87. Sams-Dodd F. Target-based drug discovery: is something wrong?. Drug Disc. Today 2005, 10:139-147.
88. Sauer U., Heinemann M., Zamboni N. Getting closer to the whole picture. Science 2007, 316:550-551.
89. Schadt E.E., Sachs A., Friend S. Embracing complexity, inching closer to reality. Sci. STKE 2005, 2005:pe40.
90. Scharfman H.E. The neurobiology of epilepsy. Curr. Neurol. Neurosci. Rep. 2007, 7:348-354.
91. Schaub C., Uebachs M., Beck H. Diminished response of CA1 neurons to antiepileptic drugs in chronic epilepsy. Epilepsia 2007, 48:1339-1350.
92. Schmidt D. Efficacy of new antiepileptic drugs. Epilepsy Curr. 2011, 11:9-11.
93. Schmidt D. Antiepileptic drug discovery: does mechanism of action matter?. Epilepsy Behav. 2011, 21:342-343.
94. Schmidt D., Löscher W. Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms. Epilepsia 2005, 46:858-877.
95. Schmidt D., Löscher W. New developments in antiepileptic drug resistance: an integrative view. Epilepsy Curr. 2009, 9:47-52.
96. Shorvon S.D. Drug treatment of epilepsy in the century of the ILAE: the second 50 years, 1959-2009. Epilepsia 2009, 50(Suppl. 3):93-130.
97. Southam E., Stratton S.C., Davies C.H. Anticonvulsant mechanisms for today and tomorrow. Drug News Perspect. 2005, 18:483-487.
98. Steinlein O.K., Mulley J.C., Propping P., Wallace R.H., Phillips H.A., Sutherland G.R., Scheffer I.E., Berkovic S.F. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat. Genet. 1995, 11:201-203.
99. Stienen M.N., Haghikia A., Dambach H., Thöne J., Wiemann M., Gold R., Chan A., Dermietzel R., Faustmann P.M., Hinkerohe D., Prochnow N. Anti-inflammatory effects of the anticonvulsant drug levetiracetam on electrophysiological properties of astroglia are mediated via TGFb1 regulation. Br. J. Pharmacol. 2011, 162:491-507.
100. Thomas E.A., Reid C.A., Berkovic S.F., Petrou S. Prediction by modeling that epilepsy may be caused by very small functional changes in ion channels. Arch. Neurol. 2009, 66:1225-1232.
101. Villoslada P., Steinman L., Baranzini S.E. Systems biology and its application to the understanding of neurological diseases. Ann. Neurol. 2009, 65:124-139.
102. von Bertalanffy L. General System Theory: Foundations, Developments, Applications 1968, Braziller, New York.
103. Wang Y.Y., Smith P., Murphy M., Cook M. Global expression profiling in epileptogenesis: does it add to the confusion?. Brain Pathol. 2010, 20:1-16.
104. Westerhoff H.V., Palsson B.O. The evolution of molecular biology into systems biology. Nat. Biotechnol. 2004, 22:1249-1252.
105. White H.S., Smith M.D., Wilcox K.S. Mechanisms of action of antiepileptic drugs. Int. Rev. Neurobiol. 2007, 81:85-110.
106. Wiener N. Cybernetics 1948, Wiley, New York.
107. Winden K.D., Karsten S.L., Bragin A., Kudo L.C., Gehman L., Ruidera J., Geschwind D.H., Engel J. A systems level, functional genomics analysis of chronic epilepsy. PLoS ONE 2011, 6(6):e20763. 10.1371/journal.pone.0020763.