Developing medical countermeasures (MCMs) to treat the acute effects of high dose, whole-body radiation exposure and trauma to save lives in radiological or nuclear incidents.
Radiological/Nuclear threats, such as radiological dispersal devices and nuclear detonations, expose individuals to ionizing radiation that damages organs, blood vessels, and bone marrow as a result of severe cellular injury. Clinically, these injuries cause Acute Radiation Syndrome (ARS). Consequences of ARS include hemorrhage, multi-organ failure, and infection, potentially leading to sepsis and/or death.
The Radiological & Nuclear Medical Countermeasures Program aims to support the advanced development of products that treat ARS and/or mechanical trauma resulting from radiological and nuclear incidents via host-directed products that can address both injury types and/or have improved storage capabilities, availability, and ease of use.
Substantial doses of ionizing radiation cause widespread cell death that leads to Acute Radiation Syndrome (ARS). Different cell types vary in their degree of sensitivity to radiation and vulnerability to cell death. Of the most sensitive and vulnerable cell populations are progenitor cells that reside within the bone marrow and give rise to red and white blood cells that circulate throughout the body. Death of progenitor cells in the bone marrow leads to a significant decrease in, and even depletion of, important immune cells required to fight pathogens that leaves affected individuals vulnerable to opportunistic infections. Platelets, which are blood cells that aid in clotting, are also detrimentally impacted by the death of progenitor cells, leading to bleeding complications. Targeting the regeneration of these cell populations is a vital treatment strategy in addressing radiation injury.
Since 2015, BARDA has supported the FDA approval of four medical countermeasures (MCMs) that target the repopulation of vascular and immune cells lost as a result of widespread cell death due to radiation. Neupogen (licensed in March 2015), Neulasta (licensed in November 2015), and Leukine (licensed in April 2018) are all commercially available countermeasures that support the accelerated recovery of neutrophils, which are white blood cells that are critical for immune defense against pathogens. Use of these products decreases the incidence of infection following radiation exposure. A fourth ARS MCM, Nplate, that addresses platelet reduction caused by radiation injury, recently gained FDA approval in January 2021 with the support of BARDA.
Moving forward, BARDA is prioritizing the development of novel and repurposed therapeutics to address blood cell (hematopoietic) injury due to radiation. These areas of development may further include technologies for reliably producing hematopoietic stem cells and their progenitors, including optimization of directed differentiation and engraftment of functional and safe hematopoietic cells.
In a radiological or nuclear mass casualty incident (MCI), severe blood loss may occur from mechanical trauma (e.g. broken bones, internal injury caused by falling or flying debris) induced by the blast. These immediate injuries will be complicated by the delayed appearance of blood disorders, such as anemia, hemorrhage, and clotting complications (coagulopathies), from exposure to ionizing radiation. Furthermore, in an MCI, fresh blood products to treat these injuries may be limited or quickly exhausted due to impeded access to the products and/or sheer magnitude of demand. Next generation blood products are a critical component to fill these blood product treatment gaps.
BARDA is prioritizing the advanced development of next generation blood products and technologies that can improve the safety and availability of blood products in MCIs by creating a surge capability (including but not limited to improving storage characteristics to allow for stockpiling) to replace fresh blood products to treat hemorrhage, and/or produce safe human red blood cell, platelet, or white blood cell products that do not induce an immune response for use in transfusing humans.
Following exposure to ionizing radiation or radioactive contaminants, physical elimination of radioactive particles, or decorporation, can be a prompt and effective treatment strategy. Currently, there are three FDA approved decorporation agents that are commercially available to limit damage from internal contamination with radioactive substances. BARDA seeks to add to this collection by supporting the development of chelators, either active or passive, of radionuclides of high threat potential. Of particular interest for advanced development are decorporation agents with additional commercial utility (e.g. lead, gadolinium) as well as formulations appropriate for all age populations, especially for children under the age of two years and others who may have difficulty swallowing solid oral dosage forms.
Elucidating the natural history of injuries resulting from radiological and nuclear events will profoundly impact the development of novel MCMs, detection methods, and diagnostic & predictive assays. Improvement of these capabilities will enable enhanced responsiveness to mass casualty events. BARDA seeks to support the development of enabling technologies that facilitate the identification of novel therapeutic targets, development of assays for diagnosis or prognosis, and/or improvement of MCM testing and screening.
CBRN has a proven track record of developing life-saving medical countermeasures. We will continue to work with partners old and new to treat or prevent the medical consequences that result from CBRN threats.
The tools and resources you need as a first responder, planner, and healthcare provider to prepare your community to respond to Chemical, Hazardous Materials, and/or Nuclear and Radiological Emergencies
Space missions expose astronauts to stressors such as radiation. As outer space is more extensively explored, space missions will become longer and expose astronauts to elevated levels of radiation.
Cellphire Therapeutics specializes in long-term stabilization and storage of platelets. BARDA is supporting its lead product, Thrombosomes, which are lyophilized (freeze-dried) activated platelets with superior storage capabilities.