# A role for pharmaceutical control of protease-activated receptor-2 for the treatment of asthma

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2024 · $716,690

## Abstract

PROJECT ABSTRACT
Asthma is a heterogenous disease that impacts ~10% of the US population. It presents as a syndrome of non-
specific airway hyperresponsiveness, inflammation and intermittent respiratory symptoms. Even though more
than half of patients receiving standard asthma medication remain uncontrolled, mainstay treatments have been
largely unchanged for several decades. While the introduction of the asthma-specific biologics in the last several
years has improved asthma for some, those treatments are extremely costly and are typically reserved for the
most severe of patients. For most asthma patients, responses are mediated by environmental allergens which
frequently possess potent protease activity. These allergen proteases provoke an increased allergen response,
in part by the direct activation of protease-activated receptor-2 (PAR2). PAR2 is a newly established target for
development of novel analgesics and therapeutics for inflammatory diseases, including asthma. We have
developed novel antagonists to PAR2 that in preliminary experiments using pre-clinical models have proven to
be effective in inhibiting or reducing the detrimental physiological changes associated with allergen-induce
asthma. Our central hypothesis for this application is: Small molecule pharmacological control of airway
epithelial and/or nociceptor PAR2 signaling provides a novel strategy for asthma protection that can be
demonstrated in vivo. We propose 3 specific aims, in which we will use a combination of in vitro and in vivo
approaches to uncover a mechanistic understanding for the roles for epithelial- and neuronal-expressed PAR2
in allergic asthma. These studies will specify pharmacological impact of PAR2 modulation on airway epithelial
cells and sensory neurons in vitro and in pre-clinical asthma models with human validation and will provide
mechanistic understanding and cellular targeting for development of novel asthma drugs for clinical trials.

## Key facts

- **NIH application ID:** 10996788
- **Project number:** 1R01AI174540-01A1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Scott Boitano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $716,690
- **Award type:** 1
- **Project period:** 2024-07-16 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996788

## Citation

> US National Institutes of Health, RePORTER application 10996788, A role for pharmaceutical control of protease-activated receptor-2 for the treatment of asthma (1R01AI174540-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10996788. Licensed CC0.

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