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Methods and compositions for control of fetal growth via modulation of relaxin

a technology of relaxin and fetal growth, which is applied in the direction of peptide/protein ingredients, immunological disorders, metabolism disorders, etc., can solve the problems of significant perinatal morbidity and mortality, interfering with the normal vascular development of the placenta, and failure of the fetus to exhibit a normal growth rate, so as to reduce the risk or incidence of spontaneous abortion

Inactive Publication Date: 2008-05-08
CORTHERA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The approach effectively increases fetal growth rates, improves placental development, and reduces the risk of complications associated with IUGR and placental insufficiency, providing a therapeutic and diagnostic tool for managing fetal growth abnormalities.

Problems solved by technology

IUGR can result from a wide variety of causes, all of which result in the failure of a fetus to exhibit a normal rate of growth.
Although some fetuses that are small for their gestational age can be simply constitutionally small and not otherwise unhealthy, other causes, such as placental insufficiency, infection, and genetic disorders, can result in significant perinatal morbidity and mortality.
It is currently believed that upregulation of s-flt, which can antagonize VEGF and PlGF activity, shifts the balance of this family toward anti-angiogenic activity, thus interfering with normal vascular development of the placenta.

Method used

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  • Methods and compositions for control of fetal growth via modulation of relaxin
  • Methods and compositions for control of fetal growth via modulation of relaxin
  • Methods and compositions for control of fetal growth via modulation of relaxin

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0259] The effect of relaxin administration on tissues thought to be targeted by relaxin during pregnancy and on the health and well-being of neonates born to mothers treated with relaxin was tested in female marmoset monkeys. Relaxin was administered during the period that spanned ovulation, implantation, and early pregnancy of the monkeys.

[0260] Animals. Female marmosets (Callithrix jacchus) were young, healthy breeders in a captive breeding colony and were housed in pairs with males under controlled environmental conditions. Under these conditions, pregnancy occurs in 90% of receptive females per cycle. Animal weights and general health were recorded immediately prior to the start of the study;

[0261] Relaxin. The recombinant human relaxin used in the study is identical to the naturally occurring, mature product of the human relaxin H2 gene and contains a 24 residue A chain and a 29 residue B chain. It was used at a concentration of either 1.5 mg / mL or 5.0 mg / mL and was formulat...

example 2

[0267] The effect of relaxin administration on (1) tissues thought to be targeted by relaxin during pregnancy and (2) on the health and well-being of neonates born to mothers treated with relaxin was tested in the female Old World cynomolgus monkey, Macaca fascicularis. Endocrine signals and the timing of implantation in these monkeys are quite similar to that seen in humans. Ovarian hormone production during the luteal phase of the cycle is similar in the macaque and humans, and both cycles end with sloughing of the endometrium. Relaxin levels in the circulation during the luteal phase and peri-implantation period approximate 50 pg / mL and 40 pg / mL in humans and macaques, respectively. Implantation occurs nine days after fertilization in the macaque while it occurs approximately two days earlier in humans, but trophoblast rescue of the corpus luteum occurs similarly in both species with increased chorionic gonadotropin production three days after implantation. Enhanced relaxin and p...

example 3

[0301] A decrease in placental hepatocyte growth factor (HGF) expression has been associated with SGA, IUGR, and preeclampsia (Dokras et al., 2001, Biol Reprod 65:1278-1288; Kauma et al., J Clin Endocrinol Metab 84:4092-4096). HIF-1α is a known upregulator of VEGF expression, as well as other angiogenic cytokines, and is also involved in increasing expression of glucose transporter-1, which is involved in glucose uptake by the developing placenta. Relaxin upregulation of HIF-1α protein expression may make HIF-1α available for activation under hypoxic conditions.

[0302] The data in this Example show that relaxin induces molecules that are deficient in IUGR and preeclampsia. Specifically, the data show that (1) relaxin increases the expression of HGF in endometrial stromal cells, as detected by quantitative PCR and ELISA; and (2) relaxin increases expression of HIP-1α in endometrial stromal cells under normoxic conditions.

[0303] Real-time quantitative RT-PCR determination of abundanc...

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Abstract

The invention relates to the method for treatment, diagnosis and prevention of diseases related to fetal growth and placental insufficiency and comprises methods including inhibiting or increasing relaxin synthesis, relaxin receptor synthesis, relaxin binding to the relaxin receptor, and relaxin receptor activity. The invention also relates to screening assays to identify compounds that modulate relaxin and / or relaxin receptor activity. The invention further relates to gene therapy methods utilizing relaxin and relaxin-related sequences for the treatment and prevention of diseases related to fetal growth and placental insufficiency.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of U.S. patent application Ser. No. 11 / 478,267 filed Jun. 28, 2006, which is a divisional of U.S. patent application Ser. No. 11 / 120,582 filed May 2, 2005 which claims benefit of the U.S. provisional patent application No. 60 / 567,353, filed Apr. 30, 2004, the disclosure of which is incorporated herein by reference in its entirety for all purposes.BACKGROUND OF THE INVENTION [0002] Intrauterine growth retardation (“IUGR”) is a syndrome whereby the size or growth rate of a fetus is unusually small for the gestational age of the fetus. Fetuses weighing below the 10th percentile for their gestational age, are by definition afflicted with IUGR. IUGR can result from a wide variety of causes, all of which result in the failure of a fetus to exhibit a normal rate of growth. Small gestational age (SGA) babies are defined as birth weight and / or length at least 2 standard deviations below the mean for gestational a...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/22C12Q1/68A61P43/00A61K38/17
CPCA61K38/2221C12Q2600/106C12Q2600/158C12Q1/6883A61P15/00A61P15/06A61P33/06A61P37/06A61P43/00A61P5/14A61P9/12Y02A50/30
Inventor UNEMORI, ELAINE
Owner CORTHERA INC
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