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Alzheimers Dement. 2009 Sep;5(5):427-32. doi: 10.1016/j.jalz.2009.06.003.

Alzheimer's disease drug development and the problem of the blood-brain barrier.

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Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.


Alzheimer's disease (AD) drug development is limited by the presence of the blood-brain barrier (BBB). More than 98% of all small-molecule drugs, and approximately 100% of all large-molecule drugs, do not cross the BBB. Although the vast majority of AD drug candidates do not cross the BBB, the present-day AD drug-development effort is characterized by an imbalance wherein >99% of the drug-development effort is devoted to central nervous system (CNS) drug discovery, and <1% of drug development is devoted to CNS drug delivery. Future AD drug development needs a concerted effort to incorporate BBB sciences early in the CNS drug discovery process. This goal can be achieved by a reallocation of resources, and an expansion of research efforts in the pure science of BBB biology and the applied science of brain drug-targeting technology.

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