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Development of an in-vitro model of human blood-brain barrier for screening of CNS drug candidates


The blood-brain barrier, separating brain from blood, strictly controls the brain micro-environment, necessary for complex neuronal signalling. To assess the potential toxicity or bioavailability of new drugs in development, pharmaceutical companies would benefit from an in-vitro model of BBB, based on brain endothelial cells in culture. Today, only preliminary models have been described, derived from primary culture of non-human brain endothelial cells. Neurotech has produced recently several immortalized human brain endothelial cell lines, the phenotype of which will be fully characterized in-vitro. Using the most differentiated cell line, representative of brain endothelium, cell culture conditions on microporous filters will be optimized to allow minimal permeability to standard molecules and maximal transendothelial electrical resistance. Cerebrus will validate this in-vitro model using a wide range of drug development candidates for the treatment of various CNS disorders: potential toxicity to and permeability through endothelial cell monolayers will be assessed and the results will be compared with those obtained in animal studies. The availability of this in-vitro model of human blood-brain barrier will constitute a valuable alternative to the use of large numbers of animals in drug screening, will significantly accelerate the CNS-oriented drug discovery and development processes, and will ultimately decrease R&D costs.

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