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The Challenges and Opportunities

  • David Borsook
  • Edward Bullmore
  • Lino Becerra
  • Richard Hargreaves
Chapter

Abstract

CNS Drug Development is difficult and costly because so many candidates fail in drug development. This chapter addresses the issue and asks whether functional imaging can provide new avenues to evaluating an objective index for drug effects and disease state. We provide an overview of specific domains in which functional imaging may be useful, including (1) dosing, (2) improved efficacy, (3) better animal–human translation (4) evaluation of direct effects of drugs on CNS, (5) pharmaco-phenotype (6) clinical phenotype (7) surrogate models and (8) potential for suggesting or defining new indications based on brain system effects. While the potential seems enormous, the adoption of new imaging technologies in drug development requires evidence-based data.

Keywords

Drug Development Target Engagement Gray Matter Loss Human Translation Traditional Clinical Trial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Beckmann N, Mueggler T, Allegrini PR, Laurent D, Rudin M (2001) From anatomy to the target: contributions of magnetic resonance imaging to preclinical pharmaceutical research. Anat Rec 265:85–100PubMedCrossRefGoogle Scholar
  2. Beckmann N, Kneuer R, Gremlich HU, Karmouty-Quintana H, Ble FX, Muller M (2007) In vivo mouse imaging and spectroscopy in drug discovery. NMR Biomed 20:154–185PubMedCrossRefGoogle Scholar
  3. Borsook D, Ploghaus A, Becerra L (2002) Utilizing brain imaging for analgesic drug development. Curr Opin Investig Drugs 3:1342–1347PubMedGoogle Scholar
  4. Borsook D, Becerra L, Hargreaves R (2006) A role for fMRI in optimizing CNS drug development. Nat Rev Drug Discov 5:411–424PubMedCrossRefGoogle Scholar
  5. CNS Market Trends, 2007 to 2010 : Key Market Forecasts and Growth Opportunities. 2007 Urch Publishing:Google Scholar
  6. Collins SD (2007) Discontinued drugs in 2006: central and peripheral nervous system drugs. Expert Opin Investig Drugs 16:1743–1751PubMedCrossRefGoogle Scholar
  7. Elmquist JK, Flier JS (2004) Neuroscience. The fat-brain axis enters a new dimension. Science 304:63–64PubMedCrossRefGoogle Scholar
  8. Gomez-Mancilla B, Marrer E, Kehren J, Kinnunen A, Imbert G, Hillebrand R, Bergstrom M, Schmidt ME (2005) Central nervous system drug development: an integrative biomarker approach toward individualized medicine. NeuroRx 2:683–695PubMedCrossRefGoogle Scholar
  9. Hurko O, Ryan Jl (2005) Translational research in central nervous system drug discovery. NeuroRx 2:671–682PubMedCrossRefGoogle Scholar
  10. Macdonald BK, Cockerell OC, Sander JW, Shorvon SD (2000) The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain 123(4):665–676PubMedCrossRefGoogle Scholar
  11. Matthews PM, Honey GD Bullmore ET (2006) Applications of fMRI in translational medicine and clinical practice. Nat Rev Neurosci 7:732–744PubMedCrossRefGoogle Scholar
  12. Obici S, Zhang BB, Karkanias G, Rossetti L (2002) Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 8:1376–1382PubMedCrossRefGoogle Scholar
  13. Palmer AM, Stephenson FA (2005) CNS drug discovery: challenges and solutions. Drug News Perspect 18:51–57PubMedGoogle Scholar
  14. Rudin M, Allegrini MT, PR BD, Rausch M (2003) Characterization of CNS disorders and evaluation of therapy using structural and functional MRI. Anal Bioanal Chem 377:973–981PubMedCrossRefGoogle Scholar
  15. Silva MD, Chandra S (2006) MRI in preclinical drug development. Methods Mol Med 124:299–322PubMedGoogle Scholar
  16. Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin PSchurmann A, Szanto I, Tschop MH, Rohner-Jeanrenaud F (2006) Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 116:1983–1993PubMedCrossRefGoogle Scholar
  17. Wise RG, Tracey I (2006) The role of fMRI in drug discovery. J Magn Reson Imaging 23:862–876PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • David Borsook
    • 1
  • Edward Bullmore
  • Lino Becerra
  • Richard Hargreaves
  1. 1.Brain Imaging CenterMcLean HospitalBelmontUSA

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