Translating promising preclinical neuroprotective therapies to human stroke trials.

Stroke is the third leading cause of mortality and carries the greatest socioeconomic burden of disease in North America. Despite several promising therapies discovered in the preclinical setting, there have been no positive results in human stroke clinical trials to date. In this article, we review the potential causes for failure and discuss strategies that have been proposed to overcome the barrier to translation of stroke therapies. To improve the chance of success in future human stroke trials, we propose that therapies be tested in stroke models that closely resemble the human condition with molecular, imaging and functional outcomes that relate to outcomes utilized in clinical trials. These strategies include higher-order, old-world, nonhuman primate models of stroke with clinically relevant outcome measures. Although stroke neuroprotection has been looked upon pessimistically given the many failures in clinical trials to date, we propose that neuroprotection in humans is feasible and will be realized with rigorous translational science.