# Therapeutic potential of a secreted phospholipase A2 Group X inhibitor in asthma

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $264,750

## Abstract

Abstract
Asthma is prevalent in the United States, affecting up approximately 8% of the population. Among asthmatic
patients, up to 60% have poorly controlled asthma despite access to a variety of targeted medications.
Eicosanoids are oxidized lipid signaling molecules, derived from arachidonic acid metabolism, and include
cysteinyl leukotrienes, prostaglandins and thromboxanes, which play an important role in asthma
pathogenesis. Pharmacological targeting of end-products of eicosanoid metabolism, primarily cysteinyl
leukotrienes, results in modest benefits in asthma. In this application, we propose to test ROC-0929, a novel
small molecule inhibitor that targets secreted phospholipase A2 group X or sPLA2-X. Phospolipases are key
enzymes involved in the release of arachidonic acid from phospholipids and have other relevant functions
including the release of other free fatty acids and lysophospholipids that serve as regulators of inflammation
relevant to asthma. We have shown that sPLA2-X is the phospholipase that is most highly elevated in asthma
and that genetic targeting of sPLA2-X is highly protective in a mouse pre-clinical model of asthma, using house
dust mite (HDM) sensitization. We hypothesize that targeting sPLA2-X with a small molecule inhibitor will
reduce immune responses and airway hyperresponsiveness (AHR). We will test this hypothesis, using a novel
small molecule inhibitor, ROC-0929, in two relevant pre-clinical models of asthma and airway
hyperresponsiveness. In the first aim, we will test the hypothesis that ROC-0929 alters intrinsic AHR to
hyperpnea, using a guinea pig model. We will further test whether ROC-0929 inhibits features of persistent
inflammation and indirect AHR in HDM sensitization, using guinea pigs. In the second aim, we will use a novel
transgenic mouse in which the human sPLA2-X gene has been knocked into the murine Pla2g10 locus to
determine whether ROC-0929 can mitigate features of airway dysfunction after the establishment of persistent
airway inflammation by HDM exposure. At the conclusion of these proof-of-concept experiments, we anticipate
sufficient data to support further development of an sPLA2-X inhibitor as a new therapeutic for asthma.

## Key facts

- **NIH application ID:** 9994609
- **Project number:** 1R21AI152488-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** William A Altemeier
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $264,750
- **Award type:** 1
- **Project period:** 2020-04-03 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994609

## Citation

> US National Institutes of Health, RePORTER application 9994609, Therapeutic potential of a secreted phospholipase A2 Group X inhibitor in asthma (1R21AI152488-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9994609. Licensed CC0.

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