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and injury technology, applied in the field of radiation exposure injury mitigation, can solve the problems of withdrawn from clinical development, ineffective in 15 to 20% of patients, etc., and achieve the effect of reducing skin injury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

The patent text shows that a substance that blocks CXCR4 can protect the skin and other tissues from damage caused by radiation.

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The stem cell factor was investigated, but was withdrawn from clinical development due to its toxicity.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
CPCA61K31/395A61K38/193A61K2300/00A61P39/00A61P43/00A61P7/00A61K39/00A61K31/4402A61K31/4709A61K31/506A61K38/10A61K38/12
Inventor KIM, JAE HOBROWN, STEPHEN L.KOLOZSVARY, ANDREW
Owner HENRY FORD HEALTH SYST
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