Abstract Details

Title Synergistic Effect of AJW200, a von Willebrand Factor Neutralizing Antibody with Low Dose Tissue Plasminogen Activator Following Embolic Stroke in Rabbits

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) IN7 - (-)

Poster/Presentation
Number 007

Objective

Background In this proof-of-concept study, which used a rigorous blinded and randomized design, we studied treatment with the anti-vWF-Ab, AJW200(0.30 mg/kg), alone or in combination with a rabbit low-dose of tPA(0.9 mg/kg) using the rabbit small clot embolic stroke model(RSCEM) with behavioral function as the endpoint. Efficacy was compared to a "positive control", a standard rabbit optimized dose of tPA(3.3 mg/kg).

Design/Methods The study used young male New Zealand white rabbits(2.2-2.5 kg). IACUC approved the procedures used in this translational study. Embolic strokes, behavioral and quantal analysis were performed as described previously (Lapchak, Translational Stroke Research 1(2), 96-107, 2010).

Results AJW200, or control IgG were administered IV 1 hour following embolization, and behavior was measured 48 hours later so that an effective stroke dose (P50) could be calculated. A beneficial treatment significantly increases P50(mg clot) compared to control. AJW200 increased P50 by 28%(p>0.05) compared to the control IgG-treated group. AJW200 plus low-dose tPA significantly increased P50 by 74%(p<0.05) and 81%(p<0.05) compared to low dose tPA or IgG, respectively, but not the AJW200 group(p>0.05). Standard dose tPA increased the P50 by 154%(p<0.05).

Conclusions In conclusion, we have demonstrated significant efficacy for the combination of AJW200 plus low dose tPA on a clinically relevant endpoint, behavior. It should be noted that while combination therapy improved behavior, it also increased the appearance of hematomas at the injection site and peripheral bleeding at incision sites. Our studies suggest that the combination therapy may be useful to improve clinical outcome in AIS patients.

Authors/Disclosures
Paul A. Lapchak, PhD, FAHA (Cedars-Sinai Medical CenterAdvanced Health Sciences Pavilion) PRESENTER	No disclosure on file
Robert L. Knobler, MD, PhD (Knobler Institute of Neurologic Disease, PC)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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