Development of gamma-tocotrienol as a radiation medical countermeasure for the acute radiation syndrome: current status and future perspectives

ABSTRACT

Introduction

The possibility of exposure to high doses of total- or partial-body ionizing radiation at a high dose rate due to radiological/nuclear accidents or terrorist attacks is increasing. Despite research and development during the last six decades, there is a shortage of nontoxic, safe, and effective radiation medical countermeasures (MCMs) for radiological and nuclear emergencies. To date, the US Food and Drug Administration (US FDA) has approved only four agents for the mitigation of hematopoietic acute radiation syndrome (H-ARS).

Area covered

We present the current status of a promising radiation countermeasure, gamma-tocotrienol (GT3; a component of vitamin E) as a radiation MCM that has been investigated in murine and nonhuman primate models of H-ARS. There is significant work with this agent using various omic platforms during the last few years to identify its efficacy biomarkers.

Expert opinion

GT3 is a newer type of radioprotector having significant injury-countering potential and is currently under advanced development for H-ARS. As a pre-exposure drug, it requires only single doses, lacks significant toxicity, and has minimal, ambient temperature storage requirements; thus, GT3 appears to be an ideal MCM for military and first responders as well as for storage in the Strategic National Stockpile.

KEYWORDS:

• Countermeasure
• gamma-tocotrienol
• mice
• proteomics
• metabolomics
• nonhuman primates
• polypharmacy
• radiation injury

Article highlight

• No radioprotector to be used for prophylaxis for either H-ARS or for GI-ARS has been approved by the US FDA.

• GT3 is a promising radiation MCM being developed under the US FDA Animal Rule as a radioprotector for H-ARS.

• The drug safety profile based on studies conducted in murine and NHP models appear encouraging.

• GT3 has been found to be efficacious in countering H-ARS in murine and NHP models when administered through subcutaneous route.

• Biomarkers are being identified using various omic platforms in both murine and NHP models.

• The drug’s efficacy in murine and NHP models, lack of side effects, and storage at ambient temperature make GT3 an ideal candidate for use by both military and first responders.

This box summarizes key points contained in the article.

Acknowledgments

The opinions or assertions contained herein are the private views of the authors and are not necessarily those of the Armed Forces Radiobiology Research Institute, or the Department of Defense. The mention of specific therapeutic agents does not constitute endorsement by the U.S. Department of Defense, and trade names are used only for the purpose of clarification. We apologize to those having contributed substantially to the topics discussed herein that we were unable to cite because of space constraints. We are thankful to Ms. Alana Carpenter for editing the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

VKS and TMS performed literature searches, drafted the manuscript, revised, and finalized for publication.

Additional information

Funding

This work was supported by funding from the Armed Forces Radiobiology Research Institute (RBB29173) awarded to VK Singh.