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Reflections on Neuroprotection Research and the Path Toward Clinical Success

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Neuroprotective Therapy for Stroke and Ischemic Disease

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Translational neuroprotection research is currently undergoing a rebirth, a much needed revival, in part due to the efficacy of both thrombolytic and endovascular procedures in subpopulations of ischemic stroke patients. Stroke is currently treated with the Food and Drug administration (FDA)-approved thrombolytic, tissue plasminogen activator (rt-PA), and can be treated with endovascular approaches using the MERCI stent retriever or the Solitaire FR stent retriever, with the application of thrombolytic (i.e., rt-PA or urokinase) prior to embolectomy for rt-PA eligible patients. Moreover, from retrospective analysis in rt-PA ineligible stroke patients, embolectomy alone has proven safe and beneficial if completed within 6 h.

Despite many decades of research into the identification and translational development of neuroprotective compounds, only few strategies have progressed into appropriately designed unbiased, randomized, placebo-controlled clinical trials. The FDA has still not been able to afford approval to a neuroprotectant to treat ischemic disease, primarily because of exaggerated overestimation of efficacy in rodent models that did not translate into efficacy in humans. During the process of developing neuroprotective compounds to treat ischemic diseases, stroke in particular, numerous problems have emerged including the absolute failure to translate preclinical animal efficacy into efficacy in stroke victims, and in some cases, both significant adverse events and unforeseen toxicities have hindered drug development and approval. This chapter describes successes and failures in the stroke neuroprotection research, provides a comprehensive tabulated assessment of select neuroprotectants that have been tested in clinical trials, and proposes recommendations and essential checklists to both guide and improve the quality of science being conducted in preclinical and translational laboratories worldwide. The ultimate goal is to reap the benefits of a worldwide concerted neuroprotection research effort to provide superior care to stroke victims.

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  1. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Suite 8305, 127S. San Vicente Blvd,, Los Angeles, CA, 90048, USA

    Paul A. Lapchak Ph.D., F.A.H.A. & Paul D. Boitano B.Sc.

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  1. Paul A. Lapchak Ph.D., F.A.H.A.
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  1. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Paul A. Lapchak

  2. Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

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Lapchak, P.A., Boitano, P.D. (2017). Reflections on Neuroprotection Research and the Path Toward Clinical Success. In: Lapchak, P., Zhang, J. (eds) Neuroprotective Therapy for Stroke and Ischemic Disease. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45345-3_1

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