# Transcriptomics and biomarkers of fetal neuroinflammation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $267,351

## Abstract

Summary
This is an administrative supplement proposal to the parent grant HD98389 (2019-24) titled “Anti-inflammatory
drug target to reduce adverse pregnancy outcomes”. The goal of the parent grant is to develop Anakinra
(recombinant human IL1receptor antagonist) as a safe and effective therapeutic for intrauterine
infection/inflammation mediated preterm labor and fetal inflammation. In the parent grant, pregnant Rhesus
macaques will be given Anakinra in a model of intrauterine inflammation (IUI). We will now leverage the
resources of the parent grant to expand the Aims of the parent grant. Fetal neuro-inflammation is associated
with later development of cerebral palsy (CP) and autism spectrum disorders (ASD) with significant medical and
public health implications. As part of the parent grant activities, we have demonstrated that inhibition of IL1
signaling using Anakinra significantly decreased fetal inflammation induced by intraamniotic injection of E. coli
LPS. We have now developed capability of extracting intact nuclei from fetal frozen brain sample and to do single
cell sequencing. Nuclear as compared to cytosolic RNA seq has the advantage of not needing protease digestion
at 37oC thereby eliminating artifactual gene expression. Furthermore, nuclear RNA seq can be done in archived
frozen brain sample thereby sparing precious animal use and reducing costs. In this administrative supplement
grant, we will test the hypothesis that inhibition of IL1 signaling by Anakinra will decrease region specific
fetal neuro inflammation induced by intraamniotic LPS. We propose doing single nuclear mRNA seq from 2
regions of the brain – the peri-ventricular white matter, and the prefrontal cortex – regions implicated in the
pathogenesis of CP and ASD. We will compare region specific single nuclear mRNA seq in three groups of
Rhesus macaque fetuses at about 80% gestation: 1) Controls – intraamniotic injection (IA) of saline, 2) IA LPS,
3) IA LPS + Anakinra. All exposures are for 16h, a time point that we previously demonstrated to be optimum for
the proposed studies. The animal resources funded by the parent grant are already available. Thus, single cell
transcriptomic studies will be greatly facilitated and feasible within the year of funding. This fetal brain
transcriptomic study will reveal mechanistic insights in the pathogenesis of neuroinflammation resulting from IUI,
and identify leads for biomarker sets for CP and ASD. The study will also further assist in pre-clinical development
of Anakinra as a therapeutic candidate for IUI.

## Key facts

- **NIH application ID:** 10175560
- **Project number:** 3R01HD098389-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** SUHAS KALLAPUR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $267,351
- **Award type:** 3
- **Project period:** 2020-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175560

## Citation

> US National Institutes of Health, RePORTER application 10175560, Transcriptomics and biomarkers of fetal neuroinflammation (3R01HD098389-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10175560. Licensed CC0.

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