Differentially expressed nucleic acids in the blood-brain...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/52 (2006.01) A61K 38/17 (2006.01) A61K 48/00 (2006.01) C07K 14/47 (2006.01) C12N 15/12 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2515603

The present invention relates to nucleic acids and polypeptides encoded thereby, whose expression is modulated in brain microvascular endothelial cells undergoing early dynamic inflammation-induced changes in blood-brain barrier functionality. Such polypeptides are referred to as lipopolysaccharide- sensitive (LPSS) polypeptides herein. These nucleic acids and polypeptides may be useful in methods for controlling blood-brain barrier properties in mammals in need of such biological effects. This includes the diagnosis and treatment of disturbances in the blood-brain/retina barrier, brain (including the eye) disorders, as well as peripheral vascular disorders. Additionally, the invention relates to the use of anti-LPSS polypeptide antibodies or ligands as diagnostic probes, as blood-brain barrier targeting agents or as therapeutic agents as well as the use of ligands or modulators of expression, activation or bioactivity of LPSS polypeptides as diagnostic probes, therapeutic agents or drug delivery enhancers.

La présente invention concerne des acides nucléiques et des polypeptides codés par ceux-ci, dont l'expression est modulée dans les cellules endothéliales microvasculaires du cerveau subissant des changements dynamiques précoces induits par inflammation dans la fonctionnalité de la barrière hémato-encéphalique. Ces peptides sont ici appelés polypeptides sensibles aux lipopolysaccharides (LPSS). Ces acides nucléiques et polypeptides peuvent être utiles dans des procédés intervenant sur les propriétés de barrière hémato-encéphalique chez les mammifères nécessitant de tels effets biologiques. Ceci comprend le diagnostic et le traitement de perturbations dans la barrière hémato-encéphalique/rétinienne, des troubles cérébraux (y compris l'oeil), ainsi que des troubles vasculaires périphériques. De plus, l'invention concerne l'utilisation d'anticorps anti-polypeptides LPSS ou de ligands en tant que sondes de diagnostic, en tant qu'agents ciblant la barrière hémato-encéphalique ou en tant qu'agents thérapeutiques, ainsi que l'utilisation de ligands ou de modulateurs d'expression, d'activation ou de bioactivité de polypeptides LPSS en tant que sondes de diagnostic, agents thérapeutiques ou facilitateurs d'administration de médicaments.

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