A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 39/395 (2006.01) A61K 38/00 (2006.01) A61P 25/28 (2006.01)
Patent
CA 2066738
An in vitro model of a blood-brain barrier comprising a porous solid support upon which is disposed an essentially confluent monolayer of brain microvascular endothelial cells in contact with agents that elevate effective cyclic AMP concentrations in endothelial cells, with or without astrocyte-derived or endothelial cell-derived conditioned medium or the equivalent so that high electrical resistance tight junctions are formed between endothelial cells, and endothelial cells exhibit peripheral phalloidin staining and E-cadherin. Also disclosed is the use of agents that reduce effective cyclic AMP concentrations or interfere with the functioning of cyclic AMP or increase effective cyclic GMP concentrations to open up blood-brain barriers in vitro and in vivo, so that drugs normally excluded by such barriers may substantially penetrate such barriers. Also disclosed are uses of the model to screen for reagents with clinical utility in disorders involving brain endothelial cells. The prevention, treatment, and amelioration of a pathology characterized by brain inflammation are described herein. Uses of agents that inhibit binding of VLA-4 to brain endothelial receptor VCAM-1 are included. These agents may be antibodies, peptides, peptidomimetics, or related compounds.
Horner Heidi C.
Porter Seth
Rubin Lee L.
Yednock Theodore A.
Athena Neurosciences Inc.
Elan Pharmaceuticals Inc.
Gowling Lafleur Henderson Llp
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