Recent achievements by AFRRI researchers include:
Demonstration that gene expression, cell function, and cell cycle of endothelial cells and hematopoietic cells are influenced by radiation and by interactions between the two cell types. These interactions involve modulation of MAPKs p38 and p44/42 (ERK1/2), growth factors, angiopoietin 2, activated caspase 3, and apoptosis. These phenomena may affect the success of therapies for acute radiation syndrome (ARS) and cancer.
Elucidation of intracellular signaling molecules involved in injury and recovery from radiation. These signals mediate effects of some of AFRRI's leading radiation countermeasure candidates. An example of this is the demonstration that delta tocotrienol protects human and mouse cells from radiation damage through suppression of IL-1β-induced NFκB/microRNA-30 signaling. Mechanistic knowledge will be required for licensure of countermeasures by the FDA.
Development of a panel of seven efficacious radiation countermeasures with low toxicity and practical routes of administration. These candidates are ready for advanced development by other DOD agencies when resources become available. All are at Technology Readiness Level (TRL) 3 or above. This is the level for which AFRRI is funded (6.2 and 6.3).
- Five of these countermeasure candidates were conceived at AFRRI, and research and development initiated at AFRRI. These are 5-AED, tocols, genistein (BIO 300), CIPRO, and ghrelin.
- Two were researched at early stages in collaboration with companies: Ex-Rad® and CDX-301.
- Three have FDA Investigational New Drug (IND) status for ARS: 5-AED, genistein (BIO 300), and Ex-Rad®.
- Six have human safety trials: 5-AED, genistein (BIO 300), Ex-Rad®, CDX-301, CIPRO, and Ghrelin.
- The seventh (tocols) has very low toxicity in non-GLP studies (administered in a manner suitable for an ARS countermeasure).
- All enhance survival in irradiated animals in robust studies repeated multiple times.
Establishment of a panel of blood biomarkers to assess severity of radiation injury and predict outcome. Rapid, easy assessments of radiation injury are required to guide medical treatment, especially in a mass casualty scenario. Successful biomarkers have been identified in a variety of species. Mathematical algorithms were developed that utilize multiple parameters to predict clinical outcome after radiation exposure. AFRRI is working with a private company to produce a portable instrument that can rapidly assess these biomarkers outside the hospital environment.
Expansion of knowledge of Vitamin E-related molecules (tocols) as radiation countermeasures. It was demonstrated that tocols can be used to mobilize blood-forming cells from bone marrow, and that these cells can be used to enhance survival after radiation exposure.
Identification of countermeasures that enhance survival in animals experiencing combined radiation injury and other injuries (“combined injury”). This work is especially challenging because most countermeasures effective against radiation alone have been ineffective against combined injury. AFRRI demonstrated success for combined injury treatment with the following agents: ciprofloxacin (CIPRO, acting via mechanisms other than its well-known antimicrobial action), ghrelin (a gastrointestinal hormone), and tocol-mobilized blood cell progenitors.
Demonstration that some metal formulations proposed for military munitions induce rhabdomyosarcoma around implanted pellets simulating shrapnel wounds.
Establishment of the minipig as a credible model for studying ARS and testing countermeasures. AFRRI's program inspired the creation of a consortium of labs around the country studying ARS in minipigs. Three other institutions have now confirmed AFRRI's finding that the natural history of ARS is extremely reproducible in minipigs. The government is now exploring the use of the minipig as a large animal model to support licensure of countermeasures by the FDA.
The institute is also engaged in education efforts, providing medical training and emergency response capabilities to manage incidents related to radiation exposure.