In a post 9-11 world, the threat of a "dirty bomb" or a radioactive attack is no longer an abstraction. In this proposal, we will address the problem of bone marrow failure caused by acute radiation poisoning. Bone marrow failure can be caused by whole body exposure to even low doses of radiation. Current treatments for radiation induced bone marrow failure include blood products, antibiotics, hematopoietic cytokines, as well as the possible use of hematopoietic cell transplantation in a select number of victims who have no other injuries. Simple, inexpensive, effective, and easily accessible therapies for bone marrow failure due to toxic radiation exposure are currently lacking. Clearly, new radiation countermeasures are needed. This proposal will examine the molecular mechanism of one such potential new therapy.
We propose that a novel therapeutic peptide, ARA 290, will provide protection to hematopoietic stem cells acutely exposed to ionizing radiation. Our preliminary experiments demonstrate that ARA 290, an 11 amino peptide, improves outcomes in a mouse model of radiation-induced bone marrow failure. However, the mechanism of protection remains unclear. ARA 290 represents an inexpensive compound that could be easily stockpiled for future emergencies and mass casualty scenarios.
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