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Selective Inhibition of GRP 94 to Treat Ocular Hypertension and Glaucoma

Award Number: R01EY036107
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Selective Inhibition of GRP 94 to Treat Ocular Hypertension and Glaucoma - Project Summary The accumulation of mutant myocillin leads to decreased aqueous humor outflow and results in ER dysfunction. Grp94 is a major chaperone localized to the ER that is responsible for modulating ER stress and the folding of select client proteins to maintain proteostasis. Through a number of key studies, it has been shown that Grp94 attempts to fold mutant myocillin, but instead co-aggregates and creates a toxic gain of function for Grp94 that results in POAG. Recently, we discovered Grp94 selective inhibitors and demonstrated both in vitro and in vivo that they reduced aggregation and restore intraocular pressure, providing a new mechanism for the treatment of POAG. Therefore, we propose in this application to optimize our lead compounds, determine their mechanism of action, and provide additional data to support their development as topically administered therapeutics not only for POAG, but also steroid-induced glaucoma.


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 = $591,767 )
2025	2025	UNIVERSITY OF NOTRE DAME DU LAC	940 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Vision Research	000	2	7/10/2025	NON-COMPETING CONTINUATION	$591,767
														Subtotal = $591,767

Issue Date FY: 2024 ( Subtotal = $617,323 )
2024	2024	UNIVERSITY OF NOTRE DAME DU LAC	836 GRACE HALL	NOTRE DAME	IN	46556	ST JOSEPH	USA	Vision Research	000	1	6/28/2024	NEW	$617,323
														Subtotal = $617,323

Grand Total All Awards = $1,209,090

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Selective Inhibition of GRP 94 to Treat Ocular Hypertension and Glaucoma

Award Number: R01EY036107

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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