9 - Using diffusion-perfusion MRI in animal models for drug development

Summary

Introduction

The development of therapies for acute ischemic stroke is a difficult venture with many potential pitfalls. Currently, the only approved therapy for acute ischemic stroke is intravenous tissue plasminogen activator (t-PA) given within 3 hours of stroke onset. The approval of rt-PA stemmed from the National Institutes of Neurological Disorders and Stroke (NINDS) trials that demonstrated a significant treatment effect with rt-PA on several different types of 90-day outcome measures and global assessment of these measures. Two other acute stroke therapy trials yielded statistically significant positive effects on the prespecified primary outcome measures. In the Stroke Therapy Ancrod Trial (STAT), ancrod, a defrinogenating agent, initiated within 3 hours of stroke onset improved outcome, but not as favorably as rt-PA given within the same time window. Another ancrod trial with a 6-hour window to the initiation of treatment was stopped and the drug has not been approved by regulatory agencies. The other positive acute stroke trial was the PROACT 2 trial that evaluated the thrombolytic agent, proUrokinase, within 6 hours of stroke onset in a group of relatively severe stroke patients with angiographically confirmed middle cerebral artery occlusion. The trial only included 180 patients and did not lead to regulatory approval. There have been a large number of other acute stroke therapy trials, both phase 2 and phase 3 trials that have not achieved a favourable outcome.