# Dexamethasone as an Effective Therapy for Ocular Injuries by Vesicating Agents.

> **NIH NIH U01** · UNIVERSITY OF COLORADO DENVER · 2020 · $727,496

## Abstract

Project Summary Abstract
Sulfur mustard (SM), nitrogen mustard (NM) and lewisite (LEW) are vesicating agents that are among the most
potent chemical weapons, and are the current focus for the development of countermeasures. In the past, lack
of NM-, SM- and LEW-induced ocular injury models to identify the mechanisms of toxicity and therapeutic
targets has been a major impediment to developing effective therapies. However, in recent years, we have
successfully developed and characterized all three vesicants (NM, SM, and LEW)-induced ocular (corneal)
injury models in vivo in rabbits, relevant to humans. Also, we identified an increased expression of COX-2 and
iNOS, VEGF, and MMP-9 as possible mediators of inflammation, neovascularization (NV) and microvesication,
respectively, in ocular injuries by these three vesicants. This is an important finding as it suggests that an
agent effective against the ocular injury induced by one of these vesicants would also be effective against the
others. Indeed, in our proof of concept efficacy studies, we demonstrated that dexamethasone (DEX, an
FDA approved drug) is an effective agent in ameliorating all three vesicants (NM, SM, LEW)-induced
ocular injuries in vivo in rabbits. This is a significant finding because the regulatory pathway for this new use
of DEX is much easier to pursue, since the new use application for DEX would be able to rely on the existing
safety and efficacy data of the reference DEX application, leading to less data needed for the application and
an easier approval pathway. An advantage of DEX, based on review by the CU technology transfer office, is
that there are no competitive intellectual property (IP) barriers to bringing this new use to market. The further
advantage of using DEX is that we do not need to generate additional IP in order to create a commercial
product, as DEX is available at a low cost from multiple sources as a generic and branded prescription drug,
and will have no shortages in times of a medical emergency. Together, based on our completed studies and
clear regulatory pathway forward, our hypothesis is that DEX has strong potential to reverse both
mustard- and arsenical-induced ocular injury, and that as a promising targeted `optimized lead'
therapeutic, it can be easily available for human use in medical emergency. Our specific aims are to: 1)
optimize dosing frequency of DEX to treat vesicating agents-induced in vivo ocular injury in rabbits; 2) evaluate
the most effective DEX treatment regimen to counteract vesicating agents-induced corneal injury in human
corneal organ culture; 3) define the molecular mechanism of DEX in rescuing vesicating agents-induced ocular
injury; and 4) develop and follow regulatory strategies for approval of DEX indication as an effective
countermeasure against vesicating agent-induced ocular injury. Completion of our aims is anticipated to
make dexamethasone ready for next stage of advanced drug development process with a clear path for...

## Key facts

- **NIH application ID:** 9783247
- **Project number:** 1U01EY030405-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Rajesh Agarwal
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $727,496
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9783247

## Citation

> US National Institutes of Health, RePORTER application 9783247, Dexamethasone as an Effective Therapy for Ocular Injuries by Vesicating Agents. (1U01EY030405-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9783247. Licensed CC0.

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