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2-HOBA for Treatment of Pulmonary Hypertension

Award Number: R41HL158393
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2022

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2-HOBA for Treatment of Pulmonary Hypertension - PROJECT SUMMARY Although the ubiquity of metabolic problems in pulmonary hypertension (PH) has been known for more than a decade, a wealth of new details on the nature of this problem presents the opportunity for intervention. A combination of experimental work in cells and animals and early trials in humans, suggests that these metabolic problems are part of the causation for PH, and that inactivation of the mitochondrial lysine deacetylase SIRT3 is a central node in regulating the metabolic defects. A vicious cycle exists in which a triggering event or mutation increases reactive oxygen species (ROS), which produces reactive lipids, which adduct and inactivate SIRT3, causing metabolic changes that result in further increased ROS. Here, we break this cycle using 2-HOBA, a small molecule which can effectively soak up reactive lipids in vivo and has positive results in safety trials for other indications in humans, with some still ongoing. Effectiveness of 2-HOBA has already been established for the prevention of PH in mice, and the mechanism suggests it should be effective for reversal. Here, we prepare for human trials of 2-HOBA by testing its efficacy for reversal of established disease in two molecularly accurate mouse models alone or in combination with metformin, and by examining serum biomarkers of disease shared between humans and mice for early indications of response which can be used to guide human trials.


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: 2024 ( Subtotal = $0 )
2024	2021	MTI BIOTECH, INCORPORATED	2711 S LOOP DR STE 4400	AMES	IA	50010	STORY	USA	Lung Diseases Research	000	1	10/12/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	MTI BIOTECH INCORPORATED	2711 S LOOP DR STE 4400	AMES	IA	50010	STORY	USA	Lung Diseases Research	000	1	12/4/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $256,580 )
2021	2021	MTI BIOTECH INCORPORATED	2711 S LOOP DR STE 4400	AMES	IA	50010	STORY	USA	Lung Diseases Research	002	1	9/14/2021	NEW	$256,580
2021	2021	MTI BIOTECH INCORPORATED	2711 S LOOP DR STE 4400	AMES	IA	50010	STORY	USA	Lung Diseases Research	001	1	9/11/2021	NEW	-$256,580
2021	2021	MTI BIOTECH INCORPORATED	2711 S LOOP DR STE 4400	AMES	IA	50010	STORY	USA	Lung Diseases Research	000	1	7/26/2021	NEW	$256,580
														Subtotal = $256,580

Grand Total All Awards = $256,580

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2-HOBA for Treatment of Pulmonary Hypertension

Award Number: R41HL158393

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2022

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