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The adult human brain in preclinical drug development

Nature Reviews Drug Discovery volume 7, pages 659–666 (2008)Cite this article

Abstract

Neurodegenerative disorders are caused by the death and dysfunction of brain cells, but despite a huge worldwide effort, no neuroprotective treatments that slow cell death currently exist. The failure of translation from animal models to humans in the clinic is due to many factors including species differences, human brain complexity, age, patient variability and disease-specific phenotypes. Additional methods are therefore required to overcome these obstacles in neuroprotective drug development. Incorporating target validation using human brain-tissue microarray screening and direct human brain-cell testing at an early preclinical stage to isolate molecules that protect the human brain may be an effective strategy.

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Figure 1: Human brain banking.
Figure 2: The drug development process: an adult human brain preclinical platform.

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Acknowledgements

This work was supported by a programme grant from the Health Research Council of New Zealand, the National Research Centre for Growth and Development, the Lynette Sullivan Huntington's disease research fund, the Alzheimer's Disease Trust, and the Marsden Fund. I would like to thank my many collaborators, postdoctoral fellows, research technicians and graduate students for their advice and help over many years, and in particular my collaborator, colleague and friend R. Faull who first introduced me to the wonders of the human brain.

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  1. Mike Dragunow is at the Department of Pharmacology and the National Research Centre for Growth and Development, Faculty of Medical and Health Sciences, The University of Auckland, 85 Park Avenue, Auckland, New Zealand. m.dragunow@auckland.ac.nz,

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DATABASES

OMIM

Alzheimer's disease

amyotrophic lateral clerosis

Huntington's disease

Parkinson's disease

stroke

FURTHER INFORMATION

Australian Brain Bank Network

Discovery-1 and MetaMorph Image Analysis

Harvard Brain Tissue Resource Center

Queen Square Brain Bank for Neurological Disorders

The Neurological Foundation of New Zealand Human Brain Bank

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Dragunow, M. The adult human brain in preclinical drug development. Nat Rev Drug Discov 7, 659–666 (2008). https://doi.org/10.1038/nrd2617

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