Developing drugs that can cross the blood-brain barrier: applications to Alzheimer's disease.
Development of therapeutics for the central nervous system is one of the most challenging areas in drug development. This is primarily because, in addition to all of the other complications one faces in developing new drugs targeting peripheral sites, one must also negotiate the blood-brain barrier (BBB). There are dozens of strategies to overcome the obstacle of the BBB, but many of these are bound to fail, barring extreme serendipity, because they are based on an inaccurate or incomplete picture of the BBB. This article therefore starts with a brief review of the BBB as it pertains to drug development. It then examines some examples of the delivery of drugs to the central nervous system that are relevant to Alzheimer's disease, placing emphasis on peptides, antibodies, and antisense oligonucleotides.
Banks
William A
WA
GRECC, Veterans Affairs Medical Center-St. Louis, and Saint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, 915 N. Grand Blvd, St. Louis, MO 63106, USA. bankswa@slu.edu
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D009479:Neuropeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D000890:Anti-Infective Agents; D002491:Central Nervous System Agents; D009479:Neuropeptides; D010455:Peptides