BPI and its congeners as radiation mitigators and radiation protectors
View Patent ↗Described herein is a method of mitigating, in a subject (individual), tissue injury resulting from exposure to radiation (accidental/unintentional or intentional, such as therapeutic), chemoradiotherapy, disease, toxin, or drug or biologic mediated therapy.
1. A method for mitigating hematopoietic tissue injury in a subject resulting from exposure to radiation, the method comprising:
administering to a subject in need thereof bactericidal/permeability increasing protein (BPI) and/or one or more of its congeners in an amount effective to mitigate hematopoietic tissue injury caused by radiation exposure of the subject, wherein the subject has a decrease in bone marrow function or a decreased blood cell count as compared to expected normal levels.
2. The method of claim 1 , wherein the hematopoietic tissue injury comprises hematopoietic toxicity.
3. The method of claim 1 , wherein the radiation exposure results from accidental exposure to radiation, chemoradiotherapy or radiotherapy.
4. The method of claim 1 , wherein one or more of the BPI congeners is selected from the group consisting of rBPI21, rBPI23, rBPI50, rBPI(10-193)ala132 and a N-terminal fragment of BPI having an approximate molecular weight of from about 20 kD to about 25 kD.
5. The method of claim 1 , further comprising administering an antibiotic.
6. The method of claim 5 , wherein the antibiotic is a quinolone antibiotic.
7. The method of claim 6 , wherein the quinolone antibiotic is selected from the group consisting of moxifloxacin, ciprofloxacin, levofloxacin, garenoxacin, and delafloxacin.
8. The method of claim 1 , wherein BPI and/or its congeners is administered between 1 day before and 2 days after exposure of the subject to the radiation exposure.
9. The method of claim 8 , wherein BPI and/or its congeners is administered within 48 hours after the radiation exposure.
10. The method of claim 1 , wherein BPI and/or its congeners is administered orally, intravenously, subcutaneously, or pulmonarily.
11. The method of claim 1 , wherein BPI and/or its congeners improves the likelihood of survival of the subject.
12. The method of claim 1 , wherein BPI and/or its congeners restores blood cell counts to normal levels.
13. The method of claim 1 , wherein the hematopoietic tissue is bone marrow.
14. The method of claim 13 , wherein the subject has a hematopoietic deficiency in one or more hematopoietic cell types or lineages.
15. The method of claim 14 , wherein the hematopoietic deficiency is one or more of: lymphopenia, myelopenia, leukopenia, neutropenia, erythropenia, megakaryopenia, a deficiency in platelets, a deficiency in monocytes, a deficiency in lymphocyctes, a deficiency in erythrocytes, deficiency in neutrophils, a deficiency in T cells, a deficiency in granulocytes, and a deficiency in dendritic cells.
16. The method of claim 1 , wherein the subject has cancer and the BPI and/or its congeners is administered at least 1 hour following radiation therapy or chemoradiotherapy, but not more than 72 hours following radiation therapy or chemoradiotherapy.
17. A method for mitigating deficiency in platelets in a subject resulting from exposure to radiation, the method comprising:
administering to a subject in need thereof bactericidal/permeability increasing protein (BPI) and/or its congeners in an amount effective to mitigate deficiency in platelets caused by the radiation exposure to the subject, wherein the BPI or its congeners is administered between 1 day before and 2 days after exposure of the subject to the radiation.