# Targeted Inhibition of Interleukin-1 beta to Prevent Preterm Birth

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $770,043

## Abstract

PROJECT SUMMARY/ABSTRACT
Preterm birth remains a significant cause of neonatal morbidity and mortality. Intra-amniotic infection and
inflammation are important triggers for early preterm birth, which is associated with fetal injury mediated by
cytokines and other inflammatory mediators in the amniotic fluid and fetus. The objective of this proposal is
to establish the efficacy and safety of a novel selective allosteric interleukin-1 receptor (IL-1R) inhibitor
(Rytvela) as an antenatal therapeutic strategy to prevent fetal injury and PTB. In pregnant mice, we have
strong evidence that Rytvela is a potent suppressor of preterm birth and fetal injury induced by either
lipopolysaccharide or lipotechoic acid. To enable translation of these discoveries to human pregnancy, we
propose to test the efficacy and determine pharmacokinetics of Rytvela in a pregnant nonhuman primate model
of preterm labor induced by Group B Streptococcus (GBS), a clinically important bacterium that colonizes the
vagina and can cause preterm labor and neonatal sepsis. Our unique chronically catheterized nonhuman primate
model has the greatest relevance to human pregnancy of any animal model and allows sampling in normally
inaccessible compartments (amniotic fluid, maternal and fetal blood) multiple times without disrupting the
pregnancy. New preliminary studies added to this resubmission demonstrate: 1) inhibition of preterm birth by
Rytvela for at least 7 days (clinically significant endpoint), 2) determination of Rytvela pharmacokinetics in a rat
model, 3) ability to quantify Rytvela using mass spectrometry in plasma for pharmacokinetics studies, and 3)
incorporation of novel technology (Digital Spatial Profiling) to study immune responses at the maternal-fetal
interface. In Aim 1, we will determine Rytvela pharmacokinetics in our NHP model and establish if IL-1 inhibition
by Rytvela delays the onset of GBS-induced preterm labor. Aim 2 will determine if IL-1 inhibition by Rytvela can
ameliorate inflammatory injury to the placenta, fetal lung and brain using three high-throughput multiplexed
analyses: 1) multidimensional flow cytometry to quantitate cell populations, 2) Digital Spatial Profiling to
interrogate immunologic protein expression and pathway activation in discrete tissues (amnion, chorion, decidua)
of the placental chorioamniotic membranes, and 3) single cell RNA-Seq for transcriptomic profiling of regulatory
gene networks within single cells in placental tissues. These experiments represent a natural progression of
preliminary studies in multiple animal models and are essential to determining whether IL-1 is a viable molecular
target for the prevention of preterm birth and fetal protection.

## Key facts

- **NIH application ID:** 10162632
- **Project number:** 5R01HD098713-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kristina M. Adams Waldorf
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $770,043
- **Award type:** 5
- **Project period:** 2020-05-11 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162632

## Citation

> US National Institutes of Health, RePORTER application 10162632, Targeted Inhibition of Interleukin-1 beta to Prevent Preterm Birth (5R01HD098713-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10162632. Licensed CC0.

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