First aid medicine to treat vesicant induced corneal injury

Active Cooperative Agreement Awarded Last action

Award ID
U01EY032973
Recipient
Awarding agency
Obligated
$5,364,570

Award facts

Assistance listing
93.310 Trans-NIH Research Support
Completion date 83% complete
Funding agency
Office of the Director National Institutes of Health, Department of Health and Human Services
Place of performance
Columbus, OH 43210, USA

Award details come from USAspending.gov.

Description

Abstract
Sulfur mustard (SM) and nitrogen mustard (NM) are potent chemical threats that cause damage to the cornea, including acute photophobia and corneal lesions followed by loss of limbal stem cells (lscs) and prolonged ulceration and vascularization. Therapeutic approaches targeting both the acute and prolonged phases of SM/NM toxicity can potentially provide effective measures to counteract corneal injuries. We provide novel findings that support the benefits of MG53, a tissue repair protein, in treating vesicant-induced corneal wounds. Compared with wild type mice, MG53-/- littermates show delayed corneal RE-epithelialization, increased vascularization and conjunctivatization following NM exposure, all hallmarks of LSC deficiency. Further, transgenic mice with sustained elevation of MG53 are resistant to NM-induced corneal injury. We find that the recombinant human MG53 protein (RHMG53) protects against injury to lscs and corneal epithelial cells to preserve cornea integrity during NM exposure. We also know that MG53 protein is naturally present in the tear film and aqueous humor, supporting the physiology of MG53 in corneal homeostasis and the safe nature of using RHMG53 to treat corneal injuries. The goal of this U01 project is to develop RHMG53 as a potential effective protein therapeutic to mitigate the acute and prolonged phases of vesicant corneal injury. We will formulate RHMG53 for ocular application as a first-aid medicine that can be stockpiled as a medical reserve and rapidly deployed to affected patients in the event of chemical threats. In vitro and EX vivo studies will be performed to elucidate the mechanistic action of MG53 in protecting against NM-induced injury to lscs and corneal epithelia. Validation studies will be conducted with RHMG53 in mouse and rabbit models of vesicant-induced corneal injuries to determine the therapeutic efficacy and safety windows of RHMG53 in rescuing cornea function. Overall, this U01 program provides a unique opportunity to advance the biology of MG53 into an important counteract therapeutic.

Transactions

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Subawards

Subrecipient Amount Awarded
Rector & Visitors Of The University Of Virginia University of Virginia will be responsible for: - rhMG53 protein production and quality control for the duration of the project. Criteria for success will… $115,186
Rector & Visitors Of The University Of Virginia $134,688
Wake Forest University Health Sciences Dr. McNutt’s lab will perform experiments at Wake Forest University. Drs. Chandler and Zhu’s labs at the Ohio State University (OSU) will first… $36,374
Battelle Memorial Institute Jill A. Harvilchuck, PhD, Site Lead/Co-Investigator (0.38 calendar months). Dr. Harvilchuck will provide oversight and direct management of the project with… $156,407
Rector & Visitors Of The University Of Virginia University of Virginia will be responsible for: - rhMG53 protein production and quality control for the duration of the project. Criteria for success will… $161,876
Rector & Visitors Of The University Of Virginia $302,514

Quick answers

Who received award U01EY032973?

U01EY032973 was awarded to The Ohio State University by National Eye Institute (National Institutes of Health) on September 30, 2022.

How much is award U01EY032973 worth?

$5,364,570 has been obligated on U01EY032973.

Which agency awarded U01EY032973?

National Eye Institute (National Institutes of Health) awarded U01EY032973, with funding from Office of the Director (National Institutes of Health).

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