Method to mitigate injury from radiation exposure

a radiation exposure and injury technology, applied in the field of radiation exposure injury mitigation, can solve the problems of withdrawn from clinical development, ineffective in 15 to 20% of patients, etc., and achieve the effect of reducing skin injury

Inactive Publication Date: 2013-02-14
HENRY FORD HEALTH SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]We have demonstrated that CXCR4 antagonist mitigates injury to skin and perhaps other tissue / organs after radiation exposure.

Problems solved by technology

Peripheral blood stem cell mobilization, which has become extremely important as a source of hematopoietic stem cells for bone marrow transplantation over the last 15 years, is generally performed using the cytokine drug, G-CSF, but is ineffective in around 15 to 20% of patients.
The stem cell factor was investigated, but was withdrawn from clinical development due to its toxicity.

Method used

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  • Method to mitigate injury from radiation exposure
  • Method to mitigate injury from radiation exposure
  • Method to mitigate injury from radiation exposure

Examples

Experimental program
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Effect test

example 1

[0020]We exposed mice to radiation, total body dose of 8 Gy at a rate of approximately 1 Gy per minute. Subsequently, days later, we administered Mozobil [I.P.] at 5 mg / kg dose as a single injection. We monitored the test mice for lethality. We found survival was significantly enhanced with Mozobil.

example 2a

CXCR4 Antagonist Reduces Lethality Following Radiation Exposure

[0021]The CXCR4 antagonist plerixafor, given after total body irradiation (TBI) to C57BL / 6 mice provides significant mitigation from TBI-induced lethality. FIG. 1 illustrates the significant enhancement in survival to an otherwise lethal radiation exposure when plerixafor was administered 3 days after the radiation.

[0022]Referring to FIG. 1, mitigation of radiation lethality by plerixafor, 5 mg / kg, I.P. increased with the duration of time delay between radiation exposure and drug administration. Survival at 30 days increased from 0% to 14% to 69% when plerixafor was administered 24 h, 48 h, and 72 h after radiation exposure, respectively. Median survival was significantly improved from 18 to beyond 30 days, when the time between radiation and drug increased from 48 to 72 h (p<0.01, Logrank).

[0023]We note that the enhanced survival after radiation of animals given plerixafor was consistent with the observation that mice e...

example 2b

CXCR4 Antagonist Reduces Lethality Following Radiation Exposure

[0024]The survival results were confirmed in a different animal strain. Median survival of Balb / c mice improved from 13 days for mice receiving 7 Gy radiation alone to 18 days for mice receiving plerixafor, 5 mg / kg, i.p., 24 hours after 7 Gy (p<0.01, Logrank).

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Abstract

Mitigating radiation induced injury to a mammal that has been exposed to radiation by administering a pharmaceutically effective amount of a composition comprising at least one CXCR4 antagonist to the mammal.

Description

[0001]This application claims the benefit of U.S. provisional patent application Ser. No. 61 / 255,619, filed Oct. 28, 2009.BACKGROUND[0002]Following a (terrorist, accident, or during radiation therapy for cancer) radiation exposure either to the whole body or localized to a region of the body, tissue / organ injury results in part because of a loss of stem cells.[0003]Peripheral blood stem cell mobilization, which has become extremely important as a source of hematopoietic stem cells for bone marrow transplantation over the last 15 years, is generally performed using the cytokine drug, G-CSF, but is ineffective in around 15 to 20% of patients. Other agents have been used to mobilize and enhance G-CSF-induced mobilization. The stem cell factor was investigated, but was withdrawn from clinical development due to its toxicity.[0004]There is a need to develop pharmacologic agents that can reduce late tissue injury including skin in the time after a radiation exposure.SUMMARY OF THE INVENTI...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/33A61P39/00A61K38/19
CPCA61K31/395A61K38/193A61K2300/00A61P39/00A61P43/00A61P7/00A61K31/4402A61K31/4709A61K31/506A61K38/10A61K38/12A61K39/00
Inventor KIM, JAE HOBROWN, STEPHEN L.KOLOZSVARY, ANDREW
Owner HENRY FORD HEALTH SYST
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