Effectiveness of NA-1, a PSD95 inhibitor, in a non-human primate model of embolic stroke

Abstract

Event Abstract Back to Event Effectiveness of NA-1, a PSD95 inhibitor, in a non-human primate model of embolic stroke Douglas J. Cook1*, L. Teves1 and Michael Tymianski1 1 Toronto Western Hospital Research Institute, Canada Introduction: NA-1 is an inhibitor of the interactions of NMDA glutamate receptors with the submembrane scaffolding protein PSD-95. Treatment with NA-1 decreases stroke volume and improves functional recovery in rodent models of stroke. NA-1 is being evaluated in an ongoing Phase II human clinical trial of its efficacy in reducing the burden of embolic strokes incurred during endovascular aneurysm repair (ENACT trial; clincialtrials.gov NCT00728182). To test whether NA-1 is neuroprotective in embolic strokes in a gyrencephalic non-human primate species we undertook a randomized, blinded, crossover trial of NA-1 vs placebo in a paradigm that simulates the ENACT trial. Methods: Ten adolescent cynomolgus macaques(2.25-4.0 kg) underwent transfemoral, right intracarotid injection of twenty 100um polystyrene spheres followed by treatment with placebo(saline) or NA-1 infused intravenously 1 hour following the embolic procedure. MRI T2 and diffusion weighted imaging(7 Tesla, Bruker Biospin) was obtained at 4, 24 hours and 4 weeks post-stroke. Raw counts and volumetric measurement of diffusion lesions were collected. Primate Stroke Scale scoring was obtained serially for 2 weeks following recovery. Following a 4-week washout period each animal was crossed over to the other treatment group and the procedure was repeated. Results: There were no differences in physiologic parameters between groups. The strokes did not cause gross motor deficits. Animals treated with NA-1 exhibited markedly reduced stroke numbers and volume as compared with placebo-treated animals with the greatest difference observed in the cortex (Figure 1). There was no carry-over effect noted with a 4-week washout. Conclusion: NA-1 significantly reduced embolic stroke number and volume in gyrencephalic non-human primates. This result supports the ENACT paradigm, and the notion that NA-1 should be tested for efficacy in reducing the burden of procedurally-induced strokes in patients. Conference: B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Cook DJ, Teves L and Tymianski M (2009). Effectiveness of NA-1, a PSD95 inhibitor, in a non-human primate model of embolic stroke. Front. Neurosci. Conference Abstract: B.R.A.I.N. platform in Physiology poster day 2009. doi: 10.3389/conf.neuro.03.2009.17.009 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Dec 2009; Published Online: 16 Dec 2009. * Correspondence: Douglas J Cook, Toronto Western Hospital Research Institute, Toronto, Canada, dj.cook@me.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Douglas J Cook L. Teves Michael Tymianski Google Douglas J Cook L. Teves Michael Tymianski Google Scholar Douglas J Cook L. Teves Michael Tymianski PubMed Douglas J Cook L. Teves Michael Tymianski Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.