ABSTRACT
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.