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Testing the Lipoxygenase Inhibitor BPN - 27332 as acute phase stroke treatment in the SPAN network

Award Number: U01NS132332
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2025
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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Testing the Lipoxygenase Inhibitor BPN - 27332 as acute phase stroke treatment in the SPAN network - The goal of this project is to evaluate a novel inhibitor of the 12/15 lipoxygenase (12/15-LOX) enzyme in preclinical rodent models of ischemic stroke within the SPAN network. To this end, BPN-27332 will be tested in comparison with other preclinical stroke treatments under rigorous conditions in multiple laboratories. 12/15-LOX has been shown to be up-regulated in the ischemic peri-infarct area in both rodents and humans. It contributes to both neuronal cell death, as well as to weakening of the blood – brain barrier and edema formation. Alox15(-/-) mice in which the gene encoding 12/15-LOX has been knocked out, are protected in models of transient focal ischemia. Through the NIH Blueprint Neurotherapeutics Program we have developed BPN-27332, a novel and highly selective inhibitor of 12/15-LOX. In a mouse model of transient focal ischemia, BPN-27332 reduces infarct size when given in the acute phase. Protection is long lasting, with significant behavioral benefits still seen four weeks after the experimental stroke with excellent ADME and PK/PD properties. We now propose to test BPN-27332 in a blinded fashion in comparison with vehicle, but also with other treatment modalities. In Aim 1, the compound is subjected to rigorous quality control measures, including verification of identity and purity by HPLC and mass spectrometry and in vitro efficacy testing. In Aim 2, the compound will be shipped to the Coordinating Center for distribution to the testing sites, where BPN-27332 will be extensively tested in rodent models of ischemic stroke. Successful completion of these studies will ready BPN-27332 for clinical trials in human patients, which will hopefully lead to a much needed new treatment option for patients with ischemic strokes.


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: 2026 ( Subtotal = $0 )
2026	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/11/2026	NON-COMPETING CONTINUATION	$0
2026	2025	LOXAGEN INC	2380 SANTA ANA ST	PALO ALTO	CA	94303	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/22/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $342,612 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/15/2025	NON-COMPETING CONTINUATION	$309,667
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	9/10/2025	NON-COMPETING CONTINUATION	-$192,784
2025	2025	LOXAGEN INC	2380 SANTA ANA ST	PALO ALTO	CA	94303	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	9/10/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$225,729
														Subtotal = $342,612

Issue Date FY: 2024 ( Subtotal = $312,234 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/26/2024	NON-COMPETING CONTINUATION	$0
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/29/2024	NON-COMPETING CONTINUATION	$312,234
														Subtotal = $312,234

Issue Date FY: 2023 ( Subtotal = $338,542 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/25/2023	NEW	$338,542
														Subtotal = $338,542

Grand Total All Awards = $993,388

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Testing the Lipoxygenase Inhibitor BPN - 27332 as acute phase stroke treatment in the SPAN network

Award Number: U01NS132332

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 07/01/2025

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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