Abstract
Topics covered include:
- Strategies to develop small- and large-mol-ecule CNS drugs capable of
crossing the blood-brain barrier (BBB)
- Interviews with leading researchers who are aggressively tackling the BBB
challenge in CNS drug discovery and development
- Analysis of results from a Blood-Brain Barrier Survey, responded to by a
range of companies involved in CNS research and drug discovery/development
CNS diseases are a major focus of the pharmaceutical industry, with CNS drugs
representing some of its most successful products. These include Pfizer' s
Zoloft (sertraline, for treatment of depression and certain types of anxiety
disorders), Lilly' s Cymbalta (duloxetine, for treatment of depression) and
Bristol-Myers Squibb' s/Otsuka' s Abilify (aripiprazole, for treatment of
bipolar disorder and schizophrenia). However, drug discovery and development
researchers experience difficulty developing CNS drugs that complete clinical
trials and win regulatory approval - especially drugs which meet major unmet
needs in the CNS area, such as Alzheimer' s disease. The vast majority of drugs
fail to cross the BBB, which is causing a major bottleneck in successful
development of CNS drug candidates.
This report reviews the discovery, design and development of small- and
large-molecule drugs that can efficiently cross the BBB. This includes more
traditional, medicinal chemistry-based methods, as well as approaches that
exploit carrier-mediated transport (CMT) and receptor-mediated transport
(RMT). Also covered in the report is use of nanoparticle technology to
enable BBB penetration. Further, the report presents in vitro and in vivo
assays as well as imaging methods to ascertain a drug' s ability to cross the
BBB and reach its target.
The report includes results of a survey of researchers and executives - from
corporate and academic organizations - who are active in the CNS drug
development area. The survey explores their involvement in BBB-related
technologies and programs. The survey results are discussed in terms of what
they reveal about the current state of BBB research and the future potential
for developing drugs that are able to cross it.
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