title: Alzheimer's disease drug development and the problem of the blood-brain barrier.
abstract: 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.
authors.affiliation: Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. wpardridge@mednet.ucla.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Pardridge
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002491:Central Nervous System Agents / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans
chemical_list: D002491:Central Nervous System Agents