HUMANIZED ANTI-L-SELECTIN MONOCLONAL-ANTIBODY DREG200 THERAPY IN ACUTE THROMBOEMBOLIC STROKE

Strategies directed against activated neutrophils have reduced ischemi a-induced brain injury. However, therapies targeted specifically again st the neutrophil adhesion protein L-selectin have not yet been examin ed in stroke. This study therefore examined the effects of a monoclona l antibody directed against L-selectin in a rabbit model of thromboemb olic stroke both with (n=16) or without (n=10) concomitant t-PA therap y. Rabbits received either the humanized monoclonal antibody DREG200 d irected against the L-selectin receptor or humanized control monoclona l antibody HuDREG55 which does not bind to rabbit L-selectin in additi on to t-PA therapy (n=8, each group). HuDREG200 (2 mg kg(-1) i. v.) wa s given as a bolus 3 h following clot embolization, followed immediate ly by a 2 h intravenous infusion of t-PA (6.3 mg kg(-1)). Without t-PA therapy rabbits received HuDREG200 (2mg kg(-1), i.v.; 0=5) or HuDREG5 5 (n=5) Ih following clot embolization. The group receiving HuDREG200 in addition to t-PA demonstrated a moderate improvement in brain infar ct size (8.4+/-2.4 vs. 13.5+/-3.5, %hemisphere, mean+/-sem), ICP (fina l reading 10.0+/-1.6 vs. 12.4+/-3.0 torr) and restoration in regional cerebral blood flow (30.2+/-7.8 vs. 21.6 +/-10.9 cc 100g(-1) min(-1)) when compared to t-PA therapy alone although statistical significance was not achieved No efficacy was demonstrated in the group receiving H uDREG200 without concomitant t-PA therapy The results suggest that the addition of a humanized anti-l-selectin monoclonal antibody HuDREG200 in combination with t-PA may further improve outcome in acute thrombo embolic stroke, although future studies are necessary to support these findings.