Wednesday, July 16, 2025 7/16/2025

Antidotes against HCI-induced chronic lung injury

Award Number: U01ES030674
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/20/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Antidotes against HCI-induced chronic lung injury - SUMMARY Exposure to hydrochloric acid (HCl) can cause severe acute and chronic, potentially lethal, pulmonary injury. Because of its frequent and multiple uses, the incidence of exposure to HCl has been increasing. Furthermore, HCl is also implicated in chemical warfare both as an initiating agent and more often as a toxic product of phosgene, phosgene oxime, Lewisite and chlorine exposure. Even though there is considerable amount of data on the acute effects of HCl, much less is known about the more severe, potentially lethal chronic sequels of exposure to HCl and no antidotes exist to the most dangerous, irreversible and potentially lethal of these effects, namely pulmonary fibrosis (PF). The ubiquitous pro-inflammatory chaperone, heat shock protein 90 (HSP90) regulates the activation of several pro-fibrotic factors and is upregulated in PF. We therefore hypothesized that HSP90 inhibitors, already in clinical trials as anti-cancer agents, may prove useful as countermeasures against HCl-induced chronic lung injury and pulmonary fibrosis (PF). In Preliminary Studies, we have described key signaling events in HCl-induced PF in mice and have demonstrated that post-treatment (beginning 24 hours after HCl administration) with the HSP90 inhibitor, AUY-922 effectively blocks the upregulation of important pro-fibrotic signals, as well as the development of both pulmonary fibrosis and chronic lung dysfunction. In the current application, we propose to expand on our initial findings in three areas: 1) identify the clinically used HSP90 inhibitor which is most effective as antidote in HCl-induced PF in mice, 2) investigate a potential therapeutic role of HSP70 in the antidotal effects of HSP90 inhibitors and 3) demonstrate the ability of HSP90 inhibitors to similarly inhibit HCl-induced PF in another animal model of HCl- induced PF, the rabbit. Results from these studies will provide needed information for the further development of a specific HSP90 inhibitor as antidote against HCl-induced lung fibrosis and chronic lung dysfunction.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$552 )
2025	2022	OLD DOMINION UNIVERSITY	HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	000	3	2/11/2025	NON-COMPETING CONTINUATION	-$552
														Subtotal = -$552

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	OLD DOMINION UNIVERSITY	HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	001	3	7/25/2023	NON-COMPETING CONTINUATION	$0
2023	2022	OLD DOMINION UNIVERSITY	HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	000	3	5/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $440,014 )
2022	2022	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	002	3	8/22/2022	NON-COMPETING CONTINUATION	$440,014
2022	2021	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	000	2	7/8/2022	NON-COMPETING CONTINUATION	$0
2022	2021	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	001	2	8/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $440,014

Issue Date FY: 2021 ( Subtotal = $452,829 )
2021	2021	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	000	2	8/18/2021	NON-COMPETING CONTINUATION	$452,829
														Subtotal = $452,829

Issue Date FY: 2020 ( Subtotal = $458,758 )
2020	2020	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Environmental Health	000	1	8/19/2020	NEW	$458,758
														Subtotal = $458,758

Grand Total All Awards = $1,351,049

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Antidotes against HCI-induced chronic lung injury

Award Number: U01ES030674

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/20/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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