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Tutorial on Drug Development for Central Nervous System

  • Yoon, Hye-Jin (Department of Neurology, Washington University School of Medicine) ;
  • Kim, Jung-Su (Department of Neurology, Washington University School of Medicine)
  • Received : 2010.10.05
  • Accepted : 2010.10.07
  • Published : 2010.12.31
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Abstract

Many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are devastating disorders that affect millions of people worldwide. However, the number of therapeutic options remains severely limited with only symptomatic management therapies available. With the better understanding of the pathogenesis of neurodegenerative diseases, discovery efforts for disease-modifying drugs have increased dramatically in recent years. However, the process of translating basic science discovery into novel therapies is still lagging behind for various reasons. The task of finding new effective drugs targeting central nervous system (CNS) has unique challenges due to blood-brain barrier (BBB). Furthermore, the relatively slow progress of neurodegenerative disorders create another level of difficulty, as clinical trials must be carried out for an extended period of time. This review is intended to provide molecular and cell biologists with working knowledge and resources on CNS drug discovery and development.

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References

  1. Lansbury, P.T., Jr. (2004). Back to the future: the 'old-fashioned' way to new medications for neurodegeneration. Nat Med 10 Suppl, S51-57. https://doi.org/10.1038/nrn1435
  2. Sams-Dodd, F. (2005). Target-based drug discovery: is something wrong? Drug Discov Today 10, 139-147. https://doi.org/10.1016/S1359-6446(04)03316-1
  3. Congreve, M., Carr, R., Murray, C., and Jhoti, H. (2003). A 'rule of three' for fragment-based lead discovery? Drug Discov Today 8, 876-877.
  4. Rees, D.C., Congreve, M., Murray, C.W., and Carr, R. (2004). Fragment-based lead discovery. Nat Rev Drug Discov 3, 660-672. https://doi.org/10.1038/nrd1467
  5. Zlokovic, B.V. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57, 178-201. https://doi.org/10.1016/j.neuron.2008.01.003
  6. Schinkel, A.H., Smit, J.J., van Tellingen, O., Beijnen, J.H., Wagenaar, E., van Deemter, L., Mol, C.A., van der Valk, M.A., Robanus-Maandag, E.C., te Riele, H.P., et al. (1994). Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77, 491-502. https://doi.org/10.1016/0092-8674(94)90212-7
  7. Kimchi-Sarfaty, C., Oh, J.M., Kim, I.W., Sauna, Z.E., Calcagno, A.M., Ambudkar, S.V., and Gottesman, M.M. (2007). A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science 315, 525-528. https://doi.org/10.1126/science.1135308
  8. Davis, M.E., and Brewster, M.E. (2004). Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov 3, 1023-1035. https://doi.org/10.1038/nrd1576
  9. Pardridge, W.M. (2006). Molecular Trojan horses for blood-brain barrier drug delivery. Curr Opin Pharmacol 6, 494-500. https://doi.org/10.1016/j.coph.2006.06.001
  10. Chico, L.K., Behanna, H.A., Hu, W., Zhong, G., Roy, S.M., and Watterson, D.M. (2009). Molecular properties and CYP2D6 substrates: central nervous system therapeutics case study and pattern analysis of a substrate database. Drug Metab Dispos 37, 2204-2211. https://doi.org/10.1124/dmd.109.028134