# Determining the Role of Creatine Kinase in Asthma

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2023 · $230,250

## Abstract

Asthma is more common in children than adults, with approximately 6.2 million children under age 18
diagnosed with asthma in the US alone. Persistence of childhood asthma has been now conclusively linked to
chronic lung function deficits that track into adult life. Understanding the natural course of childhood asthma
and preventing its persistence into adult life are tasks of paramount importance. While a significant proportion
of children with asthma overcome symptoms after the onset of puberty, the factors that confer this resilience to
persistent asthma remain largely unknown. At present, there are neither established prediction models nor
available biomarkers for early risk stratification of long-term sequelae of childhood asthma.
Recently, in a multi-cohort study we reported for the first time that serum levels and whole blood gene
expression of creatine kinase (CK) are decreased in childhood asthma. CK is an enzyme that – by catalyzing
the reversible reaction of creatine and ATP to phosphocreatine and ADP – plays a vital role in cellular energy
homeostasis and buffering. Further, we conducted experimental studies in a mouse model of allergic airway
disease induced by the common allergen, house dust mite (HDM) in the presence and absence of a
pharmacological inhibitor of CK-B. We discovered that CK-B expression significantly decreased 24 hrs after
HDM challenge, yet recovered by 5 days post challenge, suggesting its importance during the resolution
phase. Most notably, we found that HDM challenged mice in which CK-B was inhibited displayed a prolonged
period of airway hyperresponsiveness and had a major impact on the presence of mucin in the airways.
While these studies indicate for the first time a potential protective role of CK in childhood asthma, multiple
elements of this association remain to be elucidated. This proposal addresses our overall hypothesis that
factors in the asthmatic lung milieu lead to the down-regulation of CK isoforms, which in turn results in
prolonged and worse asthma phenotypes. We will investigate 3 areas of interest regarding the CK isoforms
and asthma that will lead us down the path of further mechanistic understanding: 1) expression of CK in
specific respiratory epithelial cell populations and the impact on CK levels in circulation and in the lung during
asthma, 2) the impact of specific factors in an asthmatic lung environment that may regulate CK expression
and 3) if chronically low CK in early life impacts the severity of adult-onset asthma in mice.

## Key facts

- **NIH application ID:** 10744999
- **Project number:** 1R21AI178782-01
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Julie Gunnells Ledford
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $230,250
- **Award type:** 1
- **Project period:** 2023-06-22 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10744999

## Citation

> US National Institutes of Health, RePORTER application 10744999, Determining the Role of Creatine Kinase in Asthma (1R21AI178782-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10744999. Licensed CC0.

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