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Lee et al. Vessel Plus 2021;5:8 Vessel Plus
DOI: 10.20517/2574-1209.2020.72

Review Open Access

A failure of forward translation? The case of
neuroprotection

Jin-Moo Lee , Jonathan Rosand , Carlos Cruchaga 3
1
2
1 Department of Neurology, Radiology, and Biomedical Engineering, Hope Center for Neurological Disorders, Stroke &
Cerebrovascular Center, Washington University School of Medicine & Barnes-Jewish Hospital, Saint Louis, MO 63110, USA.
2 Henry and Allison McCance Center for Brain Health, Division of Neurocritical Care and Emergency Neurology, Center for
Genomic Medicine Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT
and Harvard, Cambridge, MA 02114, USA.
3 NeuroGenomics and Informatics, Department of Psychiatry, Hope Center for Neurological Disorders, the Charles F. and Joanne
Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.

Correspondence to: Dr. Jin-Moo Lee, Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110,
660 S. Euclid Ave, Campus Box 8111, USA. E-mail: leejm@wustl.edu

How to cite this article: Lee JM, Rosand J, Cruchaga C. A failure of forward translation? The case of neuroprotection. Vessel Plus
2021;5:8. http://dx.doi.org/10.20517/2574-1209.2020.72.

Received: 16 Nov 2020 First Decision: 21 Dec 2020 Revised: 8 Jan 2021 Accepted: 19 Jan 2021 Published: 7 Feb 2021
Received: First Decision: Revised: Accepted: Published: x Academic Editors: Aaron S. Dumont, Elisa F. M. Ciceri Copy Editor: Xi-Jun Chen Production Editor: Yue-Yue Zhang

Science Editor: Copy Editor: Production Editor: Jing Yu
Abstract
More than half a century of research focused on ischemic brain injury mechanisms has failed to yield a widely
accepted neuroprotective drug for the treatment of acute ischemic stroke (AIS). The absence of a therapeutic
intervention targeted at neuroprotective mechanisms raises questions about the relevance of preclinical models in
human stroke. Indeed, this failure of forward translation (traditional bench-to-bedside research) to bring candidate
drugs into clinical use suggests that alternative or complementary approaches are needed. Here, we discuss the
potential of reverse translational research - exploring a bedside-to-bench approach - utilizing big data genomics to
discover novel AIS therapeutic targets. This approach might provide insights into new and old drug targets.

Keywords: Neruoprotection, acute ischemic stroke, genomics; NIH stroke scale

STROKE AND NEUROPROTECTION
[1,2]
Worldwide, stroke is the second leading cause of death and the most common cause of adult disability .
Recent advances in reperfusion therapies (thrombolysis and thrombectomy) have dramatically improved
acute stroke care (as discussed in other articles in this issue), impacting long term outcomes. Despite the

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
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