BPI and its congeners as radiation mitigators and radiation protectors

Patent metadata

Field	Value
Publication number	US-9770483-B2
Application number	US-201214009201-A
Country	US
Kind code	B2
Filing date	Apr 5, 2012
Priority date	Apr 5, 2011
Publication date	Sep 26, 2017
Grant date	Sep 26, 2017

Abstract

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.

First claim

We claim:

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.

Assignees

• Guinan Eva
• Levy Ofer
• Dana Farber Cancer Inst Inc
• Children'S Medical Center Corp

Inventors

• Guinan Eva
• Levy Ofer

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P39/00

  General protective or antinoxious agents · CPC title