Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015

Abstract

After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop.

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“…Furthermore, nuclear accidents, such as Chernobyl and Fukushima-Daiichi, highlight the urgency for developing radiomitigators against acute radiation exposure (DREARE). There has been intense efforts by the scientific community, spurred by several federal government initiatives, to investigate the mechanisms underlying DREARE and for developing medical counter measures to mitigate its deadly effects [8]. …”

PKCδ inhibition as a novel medical countermeasure for radiation‐induced vascular damage

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Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature

“…Better radiobiological models of the human microvasculature are urgently needed to foster the implementation of contemporary radiotherapy protocols, including those based on high doses or high LET particles. In addition, there are significant knowledge gaps in the understanding of radiobiological incidents and resulting disease processes and progression, and an equally important need to develop medical countermeasures that mitigate radiation vascular injury …”