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NeuroRx. 2005 Jan;2(1):3-14.

The blood-brain barrier: bottleneck in brain drug development.

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1
Department of Medicine, UCLA, Los Angeles, California 90024, USA. wpardridge@mednet.ucla.edu

Abstract

The blood-brain barrier (BBB) is formed by the brain capillary endothelium and excludes from the brain approximately 100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs. Despite the importance of the BBB to the neurotherapeutics mission, the BBB receives insufficient attention in either academic neuroscience or industry programs. The combination of so little effort in developing solutions to the BBB problem, and the minimal BBB transport of the majority of all potential CNS drugs, leads predictably to the present situation in neurotherapeutics, which is that there are few effective treatments for the majority of CNS disorders. This situation can be reversed by an accelerated effort to develop a knowledge base in the fundamental transport properties of the BBB, and the molecular and cellular biology of the brain capillary endothelium. This provides the platform for CNS drug delivery programs, which should be developed in parallel with traditional CNS drug discovery efforts in the molecular neurosciences.

PMID:
15717053
PMCID:
PMC539316
DOI:
10.1602/neurorx.2.1.3
[Indexed for MEDLINE]
Free PMC Article
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