Translating promising preclinical neuroprotective therapies to human stroke trials

Abstract

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.

Keywords::

• animal models
• clinical trial
• neuroprotection
• outcome assessment
• primates
• stroke
• translational research

Financial & competing interests disclosure

Michael Tymianski is a Canada Research Chair (Tier 1) in translational stroke research, and the President and CEO of NoNO Inc., a biotechnology company developed to translate neuroprotectants discovered through cellular and molecular research in his laboratory to patients. Michael Tymianski is currently funded by CIHR, the Canadian Stroke Networks, Ontario Heart and Stroke Foundation, and Heart and Stroke Foundation of Canada. Douglas Cook is a Stroke Networks Research Fellow and receives research funding from the Canadian Stroke Networks, CIHR, Heart and Stroke Foundation of Canada, the University of Toronto Department of Surgery Surgeon Scientist Program, the American Association of Neurological Surgeons, and the Congress of Neurological Surgeons. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.