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Figure 1. The failure of forward translation-neuroprotection. Five decades of translation research on acute ischemic brain injury mechanisms have failed to produce a widely accepted neuroprotective drug for the treatment of acute ischemic stroke. A: Over 1,000 drug targets have been identified, yet only 100 have been tested in clinical trials-none have proven efficacious. Thus, translation from preclinical animal models to clinical trials appears to be a bottleneck in forward translation. Alternative approaches are needed to confirm the relevance of drug targets in human stroke, or to discover novel drug targets. B: Here we explore the feasibility and effectiveness of reverse translation approaches-in particular genome-wide association studies-in their ability to confirm old drug targets or reveal novel targets.