The use of mechanistic biomarkers for evaluating investigational CNS compounds in early drug development

Current Opinion in Investigational Drugs

Volumn 11, Issue 7, 2010, Pages 795-801

  Soares, Holly D ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

biomarker; CSF; imaging; proof of mechanism; proof of pharmacology; Secretase inhibitor

Indexed keywords

3,4 DIHYDROXYPHENYLETHYLENE GLYCOL; AMINE OXIDASE (FLAVIN CONTAINING); AMYLOID BETA PROTEIN; ATOMOXETINE; BAPINEUZUMAB; CENTRAL NERVOUS SYSTEM AGENTS; CYCLIC GMP; DULOXETINE; HISTAMINE H3 RECEPTOR; NORADRENALIN; QUETIAPINE; PHARMACOLOGICAL BIOMARKER;

ANXIETY DISORDER; ATTENTION DEFICIT DISORDER; DEPRESSION; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG RECEPTOR BINDING; HUMAN; NONHUMAN; REVIEW; SCHIZOPHRENIA; ANIMAL; DRUG DEVELOPMENT; METABOLISM; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); POSITRON EMISSION TOMOGRAPHY; PROCEDURES; TRANSLATIONAL RESEARCH;

ANIMALS; BIOMARKERS, PHARMACOLOGICAL; CENTRAL NERVOUS SYSTEM AGENTS; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; DRUG DISCOVERY; HUMANS; POSITRON-EMISSION TOMOGRAPHY; TRANSLATIONAL MEDICAL RESEARCH;

EID: 77954093554     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (57)

1. Kola I: The state of innovation in drug development. Clin Pharmacol Ther (2008) 83(2):227-230.
2. Kola I, Landis J: Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov (2004) 3(8):711-715.
3. Potter WZ, Manji HK: Are monoamine metabolites in cerebrospinal fluid worth measuring? Arch Gen Psychiatry (1993) 50(8):653-656.
4. Kielbasa W, Kalvass JC, Stratford R: Microdialysis evaluation of atomoxetine brain penetration and central nervous system pharmacokinetics in rats. Drug Metab Dispos (2009) 37(1): 137-142.
5. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW: Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology (2002) 27(5):699-711.
6. Swanson CJ, Perry KW, Koch-Krueger S, Katner J, Svensson KA, Bymaster FP: Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology (2006) 50(6):755-760.
7. Keielbasa W, Bingham J, Bieck PR: Pharmacokinetic-pharmacodynamic modeling of atomoxetine in adults: Characterization of dihydroxyphenylglycol (DHPG), a pharmacological marker of norepinephrine transport (NET) inhibition, in plasma and cerebrospinal fluid. American Association of Pharmaceutical Scientists, San Antonio, TX, USA (2006):Abs 2685.
8. Spencer T, Biederman J, Wilens T, Prince J, Hatch M, Jones J, Harding M, Faraone SV, Seidman L: Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry (1998) 155(5):693-695. (Pubitemid 28225414)
9. Vincent S, Bieck PR, Garland EM, Loghin C, Bymaster FP, Black BK, Gonzales C, Potter WZ, Robertson D: Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation (2004) 109(25):3202-3207.
10. Wong DT, Robertson DW, Bymaster FP, Krushinski JH, Reid LR: LY227942, an inhibitor of serotonin and norepinephrine uptake: Biochemical pharmacology of a potential anti-depressant drug. Life Sci (1988) 43(24):2049-2057.
11. Sharma A, Goldberg MJ, Cerimele BJ: Pharmacokinetics and safety of duloxetine, a dual-serotonin and norepinephrine reuptake inhibitor. J Clin Pharmacol (2000) 40(2):161-167.
12. Lowe JA 3rd, Hou X, Schmidt C, David Tingley F 3rd, McHardy S, Kalman M, Deninno S, Sanner M, Ward K, Lebel L, Tunucci D et al: The discovery of a structurally novel class of inhibitors of the type 1 glycine transporter. Bioorg Med Chem Lett (2009) 19(11):2974-2976.
13. 3 receptor antagonism increases methylhistamine levels in the cerebrospinal fluid of dogs and healthy volunteers. Alzheimer's Association International Conference on Alzheimer's Disease, Chicago, IL, USA (2009) 15:Abs P1-264.
14. Nicholas T, Evans R, Styren S, Qiu R, Wang E, Nelson F, Le V, Grimwood S, Christoffersen C, Banerjee S, Corrigan B et al: PF-04447943, a novel PDE9A inhibitor, increases cGMP levels in cerebrospinal fluid: Translation from non-clinical species to healthy human volunteers. Alzheimer's Association International Conference on Alzheimer's Disease, Chicago, IL, USA (2009) 15:Abs PS-240.
15. Martone RL, Zhou H, Atchison K, Comery T, Xu JZ, Huang X, Gong X, Jin M, Kreft A, Harrison B, Mayer SC et al: Begacestat (GSI-953): A novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein γ-secretase for the treatment of Alzheimer's disease. J Pharmacol Exp Ther (2009) 331(2): 598-608.
16. Fleisher AS, Raman R, Siemers ER, Becerra L, Clark CM, Dean RA, Farlow MR, Galvin JE, Peskind ER, Quinn JF, Sherzai A et al: Phase 2 safety trial targeting amyloid β production with a γ-secretase inhibitor in Alzheimer disease. Arch Neurol (2008) 65(8): 1031-1038.
17. Siemers ER, Dean RA, Friedrich S, Ferguson-Sells L, Gonzales C, Farlow MR, May PC: Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-β after inhibition of γ-secretase. Clin Neuropharmacol (2007) 30(6):317-325.
18. Lanz TA, Karmilowicz MJ, Wood KM, Pozdnyakov N, Du P, Piotrowski MA, Brown TM, Nolan CE, Richter KE, Finley JE, Fei Q et al: Concentration-dependent modulation of amyloid-β in vivo and in vitro using the γ-secretase inhibitor, LY-450139. J Pharmacol Exp Ther (2006) 319(2):924-933.
19. Bateman RJ, Siemers ER, Mawuenyega KG, Wen G, Browning KR, Sigurdson WC, Yarasheski KE, Friedrich SW, Demattos RB, May PC, Paul SM et al: A γ-secretase inhibitor decreases amyloid-β production in the central nervous system. Ann Neurol (2009) 66(1):48-54.
20. Albright C, Dockens R, Olson E: BMS-708163, a potent and selective γ-secretase inhibitor, decreases CSF Aβ at safe and tolerable doses in animals and humans. Alzheimer's Association International Conference on Alzheimer's Disease, Chicago, IL, USA (2008) 14:Abs P4-412.
21. Gillman K, Starrett J, MF P, Xie K, Bronson J, Marcin L, McElhone K, Bergstrom C, Mate R, Williams R, Meredith J et al: Discovery and evaluation of BMS-708163, a potent, selective and orally bioavailable γ-secretase inhibitor. Med Chem Lett (2010):doi:10.1021/ml1000239.
22. Soares H, Raha N, Sikpi M, Liston D, Brodney M, Coffman K, Tate B, Qiu R, Wang E, Li X, Hidi R et al: Amyloid β variability and effects of γ-secretase inhibition on plasma and cerebrospinal fluid levels of amyloid β peptide in healthy volunteers. Alzheimer's Association International Conference on Alzheimer's Disease, Chicago, IL, USA (2009) 15:Abs PI-259.
23. 2 receptor occupancy, clinical response, and drug and monoamine metabolites levels in plasma and cerebrospinal fluid. A pilot study in patients suffering from first-episode schizophrenia treated with quetiapine. J Psychiatr Res (2010):doi:10.1016/j. jpsychires.2010.02.004.
24. Grimwood S, Hartig PR: Target site occupancy: Emerging generalizations from clinical and preclinical studies. Pharmacol Ther (2009) 122(3):281-301.
25. 11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with alzheimer's disease treated with bapineuzumab: A phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol (2010) 9(4): 363-372.
26. Javitt DC, Spencer KM, Thaker GK, Winterer G, Hajos M: Neurophysiological biomarkers for drug development in schizophrenia. Nat Rev Drug Discov (2008) 7(1):68-83.
27. Dunn MA, Gomes H, Gravel J: Mismatch negativity in children with autism and typical development. J Autism Dev Disord (2008) 38(1):52-71.
28. Umbricht D, Krljes S: Mismatch negativity in schizophrenia: A meta-analysis. Schizophr Res (2005) 76(1):1-23.
29. 2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (2008) 199(1):77-88.
30. Reilly JL, Lencer R, Bishop JR, Keedy S, Sweeney JA: Pharmacological treatment effects on eye movement control. Brain Cogn (2008) 68(3):415-435.
31. Ross RM, McNair NA, Fairhall SL, Clapp WC, Hamm JP, Teyler TJ, Kirk IJ: Induction of orientation-specific LTP-like changes in human visual evoked potentials by rapid sensory stimulation. Brain Res Bull (2008) 76(1-2):97-101.
32. Teyler TJ, Hamm JP, Clapp WC, Johnson BW, Corballis MC, Kirk IJ: Long-term potentiation of human visual evoked responses. Eur J Neurosci (2005) 21(7):2045-2050.
33. Davis RL: Olfactory learning. Neuron (2004) 44(1):31-48.
34. Shang Y, Claridge-Chang A, Sjulson L, Pypaert M, Miesenböck G: Excitatory local circuits and their implications for olfactory processing in the fly antennal lobe. Cell (2007) 128(3):601-612.
35. Klein T, Magerl W, Treede RD: Perceptual correlate of nociceptive long-term potentiation (LTP) in humans shares the time course of early-LTP. J Neurophysiol (2006) 96(6): 3551-3555.
36. Klein T, Stahn S, Magerl W, Treede RD: The role of heterosynaptic facilitation in long-term potentiation (LTP) of human pain sensation. Pain (2008) 139(3):507-519.
37. Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J: Induction of plasticity in the human motor cortex by paired associative stimulation. Brain (2000) 123(Pt 3):572-584. (Pubitemid 30099541)
38. Stefan K, Wycislo M, Gentner R, Schramm A, Naumann M, Reiners K, Classen J: Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training. Cereb Cortex (2006) 16(3):376-385.
39. Klein T, Magerl W, Nickel U, Hopf HC, Sandkuhler J, Treede RD: Effects of the NMDA-receptor antagonist ketamine on perceptual correlates of long-term potentiation within the nociceptive system. Neuropharmacology (2007) 52(2):655-661.
40. Pedersen LM, Gjerstad J: Spinal cord long-term potentiation is attenuated by the NMDA-2B receptor antagonist RO 25-6981. Acta Physiol (Oxford) (2008) 192(3):421-427.
41. Battaglia F, Wang HY, Ghilardi MF, Gashi E, Quartarone A, Friedman E, Nixon RA: Cortical plasticity in Alzheimer's disease in humans and rodents. Biol Psychiatry (2007) 62(12):1405-1412.
42. Gao Y, Strowbridge BW: Long-term plasticity of excitatory inputs to granule cells in the rat olfactory bulb. Nat Neurosci (2009) 12(6):731-733.
43. Turetsky BI, Hahn CG, Borgmann-Winter K, Moberg PJ: Scents and nonsense: Olfactory dysfunction in schizophrenia. Schizophr Bull (2009) 35(6):1117-1131.
44. Wilson RS, Arnold SE, Schneider JA, Boyle PA, Buchman AS, Bennett DA: Olfactory impairment in presymptomatic Alzheimer's disease. Ann N Y Acad Sci (2009) 1170:730-735.
45. Wesson DW, Levy E, Nixon RA, Wilson DA: Olfactory dysfunction correlates with amyloid-β burden in an Alzheimer's disease mouse model. J Neurosci (2010) 30(2):505-514.
46. Dumont GJ, de Visser SJ, Cohen AF, van Gerven JM: Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in healthy subjects. Br J Clin Pharmacol (2005) 59(5): 495-510.
47. Mitchell HA, Weinshenker D: Good night and good luck: Norepinephrine in sleep pharmacology. Biochem Pharmacol (2010) 79(6):801-809.
48. Schulz P, Steimer T: Neurobiology of circadian systems. CNS Drugs (2009) 23(Suppl 2):3-13.
49. A receptors in the physiology and pharmacology of sleep. Eur J Neurosci (2009) 29(9): 1779-1794.
50. A circuits in brain development and therapy. Biochem Pharmacol (2004) 68(8):1685-1690.
51. Bruns A, Kunnecke B, Risterucci C, Moreau JL, von Kienlin M: Validation of cerebral blood perfusion imaging as a modality for quantitative pharmacological MRI in rats. Magn Reson Med (2009) 61(6):1451-1458.
52. 2 nicotinic receptors. Synapse (2008) 62(3):159-168.
53. Chin CL, Tovcimak AE, Hradil VP, Seifert TR, Hollingsworth PR, Chandran P, Zhu CZ, Gauvin D, Pai M, Wetter J, Hsieh GC et al: Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI. Br J Pharmacol (2008) 153(2):367-379.
54. Martin C, Sibson NR: Pharmacological MRI in animal models: A useful tool for 5-HT research? Neuropharmacology (2008) 55(6):1038-1047.
55. Preece MA, Taylor MJ, Raley J, Blamire A, Sharp T, Sibson NR: Evidence that increased 5-HT release evokes region-specific effects on blood-oxygenation level-dependent functional magnetic resonance imaging responses in the rat brain. Neuroscience (2009) 159(2):751-759.
56. Antuono P, Jones J, Wu Z, McRea T, Franczak M, Ward DB, Li SJ: Detection of changes in cerebral blood flow perfusion following Aricept treatment in mild Alzheimer's disease subjects. Alzheimers Dement (2009) 5(4 Suppl):P66.
57. Detre JA, Wang J, Wang Z, Rao H: Arterial spin-labeled perfusion MRI in basic and clinical neuroscience. Curr Opin Neurol (2009) 22(4):348-355.