Abstract Details

Title Calibration of a Rabbit Embolic Stroke Model: A Practical Alternative for Stroke Therapy Development

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) P07 - (-)

Poster/Presentation
Number 243

Objective

Background BACKGROUND: The RSCEM was developed to incorporate stroke population heterogeneity and a clinical rating endpoint based upon NIHSS. Subjects are rated for clinical function, and a quantal analysis method is used to correlate clot burden in brain with behavior. A P50 value (mg), neurologic dysfunction in 50% of a group of animals is generated and compared with control. A statistically significant increase in P50, compared to control is indicative of clinical improvement.

Design/Methods DESIGN/METHODS: All methods used for the screening of proposed "neuroprotective" drugs and "devices" have been described in detail (references 2 and 3).

Results RESULTS: In the RSCEM, tPA and NXY-059 improve clinical function when given 1-1.5 hours following embolization(1-3) and up to 1 hour after a stroke(3), respectively. In patients rt-PA is effective within 3-4.5 hours after stroke onset. [tPA, 3-fold difference in therapeutic window (TW) between species], and in the SAINT II trial, NXY-059 was not efficacious when given within 3.76 hours. The presentation will also present correlative data for transcranial laser therapy, as well as other strategies studied in both the RSCEM and patients(3).

Conclusions CONCLUSIONS: Correlative data for diverse "neuroprotective" strategies suggests that efficacy observed 1-1.5 hour post-embolization in the RSCEM may represent 2.5-3 hours in stroke patients. Using a conservative TW ratio between the RSCEM and stroke patients, a minimum threshold of 1.5 hours in the RSCEM would allow for translation of a novel neuroprotective therapy in AIS patients when administered ?3 hours. Currently, the RSCEM is the only translational model where a TW correlation exists. (1)NEJM 333, 1581-1587,1995); (2)Science, 230, 1289-1292,1985); (3)Translational Stroke Research: From Target Selection to Clinical Trials. Springer, Chapter 27, p.541-84,2012.

Authors/Disclosures
Paul A. Lapchak, PhD, FAHA (Cedars-Sinai Medical CenterAdvanced Health Sciences Pavilion) PRESENTER	No disclosure on file
Mark S. Freedman, MD, FAAN (University of Ottawa)	Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.

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