Inhibiting granulocyte macrophage-colony stimulating factor (gm-csf) prevents preterm birth

a technology of granulocyte macrophage and stimulating factor, which is applied in the field of mammals' methods of treating pregnant women, can solve the problems of lack of progress, 3.1 million neonatal deaths annually, and neonatal morbidity and mortality, and achieve the effect of reducing, preventing or delaying preterm birth

Pending Publication Date: 2021-09-30
UNIV OF CONNECTICUT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The use of GM-CSF inhibitors effectively decreases the concentration of GM-CSF in serum and amniotic fluid, reducing the incidence of preterm birth and modulating macrophage activity, thereby preventing inflammation-induced preterm birth.

Problems solved by technology

In the United States, preterm birth remains the leading cause of neonatal morbidity and mortality, and worldwide complications from preterm birth result in 3.1 million neonatal deaths annually.
This lack of progress reflects a poor understanding of the mechanisms and molecules that mediate preterm birth.

Method used

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  • Inhibiting granulocyte macrophage-colony stimulating factor (gm-csf) prevents preterm birth
  • Inhibiting granulocyte macrophage-colony stimulating factor (gm-csf) prevents preterm birth
  • Inhibiting granulocyte macrophage-colony stimulating factor (gm-csf) prevents preterm birth

Examples

Experimental program
Comparison scheme
Effect test

example 1

LPS Activates Release and Upregulates GM-CSF in Cervical Epithelial Cells and AF-MSCs

[0069]Treatment with LPS resulted in an increase in GM-CSF concentrations after 24 hours in ectocervical cells (p<0.0001), endocervical cells (p<0.0005), and AF-MSCs (p<0.01) as measured by ELISA. Expression of GM-CSF by real time qPCR increased in ectocervical cells (p<0.0005), endocervical cells (p<0.01), and AF-MSC's (p<0.0001) (FIGS. 1-6). Thus, LPS increases the concentration and gene expression of GM-CSF from cervical epithelial and AF-MSC's.

example 2

Treatment with LPS did Not Increase LDH

[0070]While exposure to LPS leads to an increase in GM-CSF concentration, LPS had no effect on the concentration of LDH compared to controls in AF-MSCs after 24 hours (data not shown) using the LDH assay (p=0.61). This finding is consistent with previous evidence that LPS does not induce cell death in ectocervical and endocervical cells.

example 3

LPS Increases Expression of GM-CSF in the Mouse Cervix and Uterus

[0071]GM-CSF expression was increased in the cervix and uterus of mice treated with an intrauterine injection of LPS compared to control mice that received saline (p<0.005, FIGS. 7 and 8). Thus, LPS is a potent promotor of GM-CSF expression.

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Abstract

A method of treating a pregnant female subject includes administering to the pregnant female subject an effective amount of a Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) inhibitor, wherein the effective amount of the GM-CSF inhibitor is effective to reduce, prevent or delay preterm birth.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of U.S. application Ser. No. 16 / 655,733 filed Oct. 17, 2019, which claims priority to U.S. Provisional Application 62 / 746,626 filed on Oct. 17, 2018, which are incorporated herein by reference in their entirety.FIELD OF THE DISCLOSURE[0002]The present disclosure is related to methods of treating pregnant mammals to reduce, prevent, or delay preterm birth.BACKGROUND[0003]In the United States, preterm birth remains the leading cause of neonatal morbidity and mortality, and worldwide complications from preterm birth result in 3.1 million neonatal deaths annually. Despite the short- and long-term health consequences of preterm birth and the sizeable health care costs, research efforts thus far have resulted in marginal improvements on the preterm birth rate. This lack of progress reflects a poor understanding of the mechanisms and molecules that mediate preterm birth. Spontaneous preterm birth is considered a ...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): C07K16/24A61K38/16A61P15/06C12N15/113
CPCC07K16/243A61K38/16A61K2039/505C12N15/1136A61P15/06C07K2317/76A61K39/3955A61K2300/00
InventorNOLD, CHRISTOPHERVELLA, ANTHONY
OwnerUNIV OF CONNECTICUT