Cel
The blood-brain barrier (BBB), separating brain from blood (as well as the bloodretinal barrier (BRB) between retina and blood) strictly controls the brain microenvironment, necessary for complex neuronal signalling. To assess the potential neurotoxicity or cerebral bioavailability of new drugs in development, academic groups and pharmaceutical companies would benefit from an in vitro model of human BBB, based on human brain endothelial cells in culture. Today, only preliminary models have been described, derived from primary cultures of non-human brain endothelial cells or from peripheral endothelial cell lines. The purpose of the present proposal is therefore to determine the extent to which immortalised human brain endothelial cell lines can be used for the development of an in vitro model of human BBB. (Since BRB characteristics are very close to those of BBB, this would constitute also an in vitro model of human BRB). This standardised model will constitute a valuable alternative to the current 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 in pharmaceutical industry.
Five contractors (two SMEs and three academic groups) constitute the proposing consortium. Two of the academic groups have top expertise in the biology of the BBB and have previously developed immortalised rat brain endothelial cell lines, the third is a world leader in the field of cell-cell endothelial junctions and vascular endothelial physiology. The two industrial collaborators are unique in Europe among Biotech companies in their specific expertise respectively in the establishment and genetic engineering of brain endothelial cell lines and in the CNS drug discovery and assessment of cerebral bioavailability. The Preparatory Award obtained by the two SMEs has allowed a feasibility study to be carried out in support of this RTD proposal.
The overall strategy will be to use an immortalised human brain endothelial cell line, recently produced by some of the consortium partners, or other human brain endothelial cell lines to be produced, and to grow and characterise them as monolayers on semi-porous membranes in various culture conditions. This new model of human BBB will be validated by measures of transendothelial electrical resistance and permeability to standard molecules and CNS drugs, which will be compared with the corresponding in vivo data. The model will be further improved by genetic engineering of the cells for higher expression of BBB-specific proteins known as key players in BBB assembling and function.
The final goal will be to have obtained and tested an immortalised human brain endothelial cell line which is a candidate for large scale production and industrial use as an in vitro model of human BBB. This, the consortium believes, is innovative, feasible and will provide commercial opportunities as a valuable alternative to the use of animals for screening of CNS drug candidates or gene therapy vectors for drug delivery to the brain.
Dziedzina nauki (EuroSciVoc)
Klasyfikacja projektów w serwisie CORDIS opiera się na wielojęzycznej taksonomii EuroSciVoc, obejmującej wszystkie dziedziny nauki, w oparciu o półautomatyczny proces bazujący na technikach przetwarzania języka naturalnego.
Klasyfikacja projektów w serwisie CORDIS opiera się na wielojęzycznej taksonomii EuroSciVoc, obejmującej wszystkie dziedziny nauki, w oparciu o półautomatyczny proces bazujący na technikach przetwarzania języka naturalnego.
- medycyna i nauki o zdrowiumedycyna klinicznafarmakologia i farmacjaopracowywanie leków
- medycyna i nauki o zdrowiubiotechnologia medycznainżynieria genetycznaterapia genowa
- nauki przyrodniczenauki biologicznebiochemiabiocząsteczkibiałka
- medycyna i nauki o zdrowiumedycyna klinicznaokulistyka
- medycyna i nauki o zdrowiumedycyna klinicznafizjologia
Aby użyć tej funkcji, musisz się zalogować lub zarejestrować
Zaproszenie do składania wniosków
Data not availableSystem finansowania
CSC - Cost-sharing contractsKoordynator
91893 Orsay
Francja