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Modelling of the Blood–Brain Barrier in Drug Discovery and Development |
InterAction Meeting Session, Bryn Mawr, Philadelphia, USA
Wednesday 14 October 2009
chaired by Romeo Cecchelli (Université Lille Nord de France) Bio....
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The blood-brain barrier (BBB) is a dynamic interface which, by regulating the exchange of substances between blood and brain, maintains optimal conditions for neuronal and glial function. Unfortunately, the same mechanisms can also prove to be formidable hurdles in drug development and the value of many promising drug candidates is diminished by the presence of this barrier, which possess both structural and enzymatic components at the level of the cerebral capillaries. Furthermore, the BBB is also implicated in pathologies such as neurodegenerative disorders (e.g. Alzheimer´s and multiple sclerosis), stroke and Epilepsia as well as in infectious processes and inflammatory pain.
By modelling the BBB, it is possible to make predictions about brain uptake of potential drug candidates and to develop strategies aiming at delivering drug to the CNS.
In addition, strategies to restore or protect the functionality of the BBB in various CNS pathologies in order to maintain brain homeostasis and normal signalling between brain cells may be of important therapeutic value. Therefore, an integrative use of in vitro BBB models and in vivo techniques (together with human clinical data) is likely to be of key importance in the development of CNS therapeutics as they enable to study the effect of therapeutic interventions at the level of the cerebral capillaries.
Finally, in vitro BBB models, makes it possible to evaluate whether a compound's interaction with brain endothelium is likely to compromise its functionality or is likely to reach and interfere with glial cells. Such data may enhance the value of the toxicological results generated in brain cells in the assessment of risk and safety in humans. Within the framework of the European Centre for Validation of Alternative Methods (ECVAM), activities are ongoing to validate procedures and experimental designs of high-throughput BBB cell models, enabling generated data to be used to assess potential toxicity problems related to the brain endothelium and associated cells.
In this session aspects of the plethora of BBB models that exist today and their applications in drug discovery will be discussed.
Presenters & Discussions Leaders
Stefan Lundquist (AstraZeneca), The Blood-Brain Barrier in the CNS Drug Discovery Process Abstract & Bio....
Reinhard Gabathuler (AngioChem), Angiopeps: a New Peptide Family for the Transport of Small and Large Molecules to the Brain Abstract & Bio....
Maxime Culot (University of Lille), In vitro Blood-Brain Barrier Models for High Throughput Toxicological Screening Abstract & Bio....
Damir Janigro (Cleveland Clinic Foundation), Drug Metabolism at the Human Epileptic Blood-Brain Barrier: In situ and in vitro Abstract & Bio....
Marie-Pierre Dehouck (University of Lille), Cell-cell interaction at the Neurovascular Unit (NVU) in Physiological and Pathological Conditions Abstract & Bio....
Pierre-Olivier Couraud (Institut Cochin), An Immortalized Human Brain Endothelial Cell Line as a Model of Human Blood-Brain Barrier for Drug Screening and Pharmacological studies Abstract & Bio....
Anna Seelig (University of Basel), Experimental and Computational Prediction of Blood-Brain Barrier Permeation Abstract & Bio....
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