The field of neuroprotection after brain injuries has been littered with failed clinical trials. Finding a safe and effective treatment for acute traumatic brain injury remains a serious unmet medical need. Repurposing drugs that have been in use for other disorders is receiving increasing attention as a strategy to move candidate drugs more quickly to trial while reducing the very high cost of new drug development. This paper describes our own serendipitous discovery of progesterone's neuroprotective potential, and the strategies we are using in repurposing and developing this hormone for use in brain injuries-applications very different from its classical uses in treating disorders of the reproductive system. We have been screening and testing a novel analog that maintains progesterone's therapeutic properties while overcoming its physiochemical challenges, and testing progesterone in combination treatment with another pleiotropic hormone, vitamin D. Finally, our paper, in the context of the problems and pitfalls we have encountered, surveys some of the factors we found to be critical in the clinical translation of repurposed drugs. This article is part of the Special Issue entitled 'Drug Repurposing: old molecules, new ways to fast track drug discovery and development for CNS disorders'.
Keywords: Combination therapy; Progesterone; Progesterone analogs; Repositioning; Repurposing; TBI; Vitamin D hormone.
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