The threat of radiological and nuclear accidents or attacks demands for effective radiation medical countermeasures (MCM) able to mitigate and treat the effects of exposure to ionizing radiations. Hematopoietic acute radiation syndrome (HRAS) and cutaneous radiation syndrome (CRS) pose severe, life-threatening risks to exposed individuals. Currently no effective radio-mitigator (to be administered after radiation exposure but prior to tissue toxicity manifestation) or radio-therapeutic (to be administered after tissue toxicity manifestation) has yet received FDA approval. Intravenous injectable Fibrinogen-coated Albumin nano-Spheres (FAS) are nanometer-sized spheres, originally developed by Fibroplate to augment hemostatic functions in multiple clinical settings. Preliminary studies conducted on irradiated rodents suggested that FAS administered after ionizing radiation exposure has a unique multi-valent radiation MCM potential to: i) accelerate healing of ulcerated, necrotic tissues arising from CRS (chronic wounds), ii) increase white blood cells count to counter neutropenia induced by HRAS, iii) augment hemostatic functions to mitigate the effects of thrombocytopenia induced by HRAS. Remarkably, these studies have indicated that FAS might be able to promote mobilization of progenitor cells of various lineages: this would explain the ability of FAS in increasing white blood cells count and promoting the coordinated developments of multiple tissues, facilitating chronic wound healing. By taking advantage of this knowledge, Fibroplate, Inc. proposes to further investigate the efficacy of FAS as radio-therapeutic for radiation skin ulcer (RSU) arising from CRS in a RSU rat model; if successful, FAS could be administered as a treatment only to the individuals which actually develop ulcers after exposure to high radiation doses. In case of nuclear emergency, in fact, having a single MCM that is easy to store, transport, administer and effective both before and after the manifestation of toxicity effects, would represent a radiation MCM of tremendous efficacy. In this SBIR Phase I project we aim to accomplish two objectives: 1) demonstrate the efficacy of FAS as radio-therapeutic for RSU: FAS will be administered as a treatment, i.e. after the ulcer appears, instead of using it as a mitigation measure; 2) to confirm the mobilization of stem cells induced by FAS, thus allowing to delve deeper into FAS mechanism of action, in view of future IND and FDA submission. This work will be preparatory of Phase II, where a complete preclinical study compliant with FDA animal efficacy rule, for determination of metabolism, dose and dose scheduling, will be carried out to obtain IND and FDA licensure for FAS as a unique radio-mitigator and radio-therapeutic product. Fibroplate aims to develop FAS as a strategic new, multi-valent and easy-to-use MCM, and to target other market segments such as the one of nuclear power plants and radiotherapy patients, demanding effective MCM to mitigate and treat effects of radiation exposure.
Public Health Relevance Statement: NARRATIVE The availability of medical countermeasures able to treat radiation skin ulcers caused by cutaneous radiation syndrome is of extreme importance in case of radiological/nuclear emergencies. Fibrinogen-coated Albumin Spheres (FAS) is a safe, multi-valent, biological product with long shelf life and ease of administration. FAS can potentially become the first medical countermeasure able to both mitigate and treat multiple radiation syndromes.
Project Terms: Acute; Address; Albumins; animal efficacy; Animal Model; Antibodies; Authorization documentation; base; Biological Markers; Biological Products; Bleeding time procedure; Blood; blood perfusion; Blood Platelets; CD34 gene; Cells; Characteristics; chronic wound; Clinical; Control Groups; cost; Cutaneous; cytokine; Development; Disease; Dose; Emergency Situation; Event; Exposure to; Fibrinogen; Future; Government Agencies; healing; Hematopoietic; Hematopoietic Stem Cell Mobilization; Hemorrhage; Hemostatic function; Human; Immune; Immunologics; improved; Individual; Infection; Injectable; Injury; Intravenous; Ionizing radiation; Knowledge; Leg; Leukocytes; Licensure; Life; Link; Measures; Medical; medical countermeasure; Metabolism; Modeling; Mus; nanoscale; Nanosphere; Necrosis; Needle biopsy procedure; Neutropenia; neutrophil; novel; Nuclear; Nuclear Accidents; Nuclear Power Plants; Nuclear Radiology; Nuclear Warfare; Outcome; overexpression; Patients; Phase; phase 1 study; Platelet Count measurement; Population; preclinical study; Privatization; Property; Public Health; Radiation; Radiation Accidents; Radiation Dose Unit; radiation effect; Radiation exposure; Radiation Injuries; radiation mitigator; Radiation Syndromes; Radiation therapy; Radiation Toxicity; radiological attack; RAS genes; Rattus; Red Blood Cell Count; repaired; Research; Risk; Rodent; Safety; Saline; Sampling; Schedule; Site; Skin; skin lesion; Skin Ulcer; Small Business Innovation Research Grant; Source; Stains; Stem cells; Syndrome; Temperature; Testing; Therapeutic; Thrombocytopenia; Tissues; Toxic effect; Ulcer; Weight; White Blood Cell Count procedure; Work; Wound Healing
