# A Safer Glucocorticoid to Treat Neonatal Lung Injury with Limited Adverse Neurologic Effects

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $606,797

## Abstract

Bronchopulmonary dysplasia (BPD) remains a significant complication of prematurity
affecting nearly 70% in infants born ≤28 weeks. Current pharmacologic strategies to
mitigate the development and progression of BPD include administration of long-acting
synthetic glucocorticoids (sGCs) such as dexamethasone (Dex). Several randomized
clinical trials establish that sGC therapy targeted to preterm infants with evolving lung
injury decreases BPD risk substantially, but encumber significant risks related to adverse
somatic growth and long-lasting alterations in brain structure and function. Therefore,
there remains an urgent need for GC pharmacotherapy for BPD in neonates that will
provide beneficial anti-inflammatory and lung maturation effects, but limited adverse
effects on the brain. Ciclesonide (CIC) is a new generation inhaled sGC currently
approved for the treatment of asthma and allergic rhinitis that does not cause systemic
adverse effects often observed with other sGCs. Clinical trials also demonstrate no
adverse effects of CIC beyond placebo in 2-year olds. We hypothesize that CIC will
attenuate hyperoxia-mediated acute lung injury in neonates but NOT trigger the
demyelination, astrogliosis, microglia activation or neuronal damage in neonatal brain
caused by systemically administered sGCs such as Dex. Three Specific Aims are
proposed to test this hypothesis with a multi-disciplinary team possessing the ability to
simultaneously investigate in vitro mechanisms and highly relevant rodent models of
neonatal lung injury. Aim 1 will determine the mechanisms by which CIC prevents
hyperoxia-induced acute lung injury and alveolar remodeling in experimental BPD. Aim 2
will identify the transcriptomic responses to CIC within individual cell types of neonatal
mouse lungs using scRNA-Seq. Aim 3 will compare the acute and long-term
consequences of neonatal Dex versus CIC exposure on brain architecture and behavior.
This study has potential to identify CIC as an effective sGC therapy for BPD with brain-
sparing effects, addressing the current dearth of therapies to prevent and/or treat BPD in
preterm infants.

## Key facts

- **NIH application ID:** 10312167
- **Project number:** 1R01HD104215-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Donald B DeFranco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $606,797
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312167

## Citation

> US National Institutes of Health, RePORTER application 10312167, A Safer Glucocorticoid to Treat Neonatal Lung Injury with Limited Adverse Neurologic Effects (1R01HD104215-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10312167. Licensed CC0.

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