The Role of Blood-Brain Barrier Studies in the Pharmaceutical Industry

作者：Andreas Reichel · 发表于：Current Drug Metabolism · 年份：2006 · DOI：10.2174/138920006775541525 · 被引用次数：144 · 研究领域：Pharmacogenetics and Drug Metabolism、Chemical Reactions and Isotopes、Drug Transport and Resistance Mechanisms

The blood-brain barrier (BBB) remains one of the greatest challenges for the discovery and development of treatments for CNS disorders, which to this day remains one of the riskiest disease areas in terms of clinical success rates. Although the BBB is currently seen predominantly as a permeability obstacle for CNS drug delivery, it is becoming increasingly clear that the BBB has many more implications for the pharmaceutical industry impacting on CNS pharmacology and pathology, CNS pharmacokinetics and pharmacodynamics, and adverse CNS effects, to name but a few areas. The present review does not intend to summarize the activities in the field of BBB research per se, which has been accomplished by a number of excellent recent reviews, but instead to provide an overview of the role of BBB studies from a pharmaceutical industry perspective. This review will elaborate on the specific needs in terms of BBB-related issues across the different drug discovery and development phases, i.e. target identification and validation, lead generation and optimization, candidate selection and profiling, preclinical development and clinical studies. The specific approaches taken will be discussed in terms of specific requirements, questions to be asked, feasibility, interpretability, and impact. It becomes clear that few of the existing BBB models fully meet the requirements of the industrialized drug discovery process, highlighting the need for an array of new or modified tools and approaches t...