R42HL158393
Project Grant
Overview
Grant Description
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. Our preliminary studies show that 2-HOBA is a safe compound and in IND enabling animal toxicity and human safety trials, and shows great promise in treating the core molecular defects in PH.
Our preliminary data and phase I studies demonstrate not only clear positive impact on reducing pulmonary vascular resistances in Group I and II PH, and both cytokine and molecular biomarkers of disease, but also indicate the potential for a substantial positive effect on heart function under load stress.
In this phase II project, we will establish the remaining data needed to proceed to commercialization through the following aims:
1) We will test the safety and molecular efficiency of 2-HOBA in PH patients in a small open label mechanistic pilot trial with two weeks of 2-HOBA exposure.
2) We will demonstrate efficacy of 2-HOBA in improving function of the right ventricle under stress in a well-established sheep model.
3) We will test effectiveness of 2-HOBA alone and in the context of standard-of-care in mouse models and large animals.
2-HOBA is an entirely new approach to solving a molecular problem that several existing clinical trials and case reports have tried to resolve, but so far with limited success. The specific mechanism of action of 2-HOBA should allow it to succeed where other interventions have failed.
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. Our preliminary studies show that 2-HOBA is a safe compound and in IND enabling animal toxicity and human safety trials, and shows great promise in treating the core molecular defects in PH.
Our preliminary data and phase I studies demonstrate not only clear positive impact on reducing pulmonary vascular resistances in Group I and II PH, and both cytokine and molecular biomarkers of disease, but also indicate the potential for a substantial positive effect on heart function under load stress.
In this phase II project, we will establish the remaining data needed to proceed to commercialization through the following aims:
1) We will test the safety and molecular efficiency of 2-HOBA in PH patients in a small open label mechanistic pilot trial with two weeks of 2-HOBA exposure.
2) We will demonstrate efficacy of 2-HOBA in improving function of the right ventricle under stress in a well-established sheep model.
3) We will test effectiveness of 2-HOBA alone and in the context of standard-of-care in mouse models and large animals.
2-HOBA is an entirely new approach to solving a molecular problem that several existing clinical trials and case reports have tried to resolve, but so far with limited success. The specific mechanism of action of 2-HOBA should allow it to succeed where other interventions have failed.
Awardee
Funding Goals
THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Ames,
Iowa
500108656
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 163% from $1,173,060 to $3,088,886.
MTI Biotech was awarded
2-HOBA for Pulmonary Hypertension Treatment
Project Grant R42HL158393
worth $3,088,886
from National Heart Lung and Blood Institute in September 2021 with work to be completed primarily in Ames Iowa United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.837 Cardiovascular Diseases Research.
The Project Grant was awarded through grant opportunity PHS 2022-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Required).
SBIR Details
Research Type
STTR Phase II
Title
2-HOBA for Treatment of Pulmonary Hypertension
Abstract
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 our preliminary studies show that 2-HOBA is a safe compound and in IND enabling animal toxicity and human safety trials and shows great promise in treating the core molecular defects in PH. Our preliminary data and Phase I studies demonstrate not only clear positive impact on reducing pulmonary vascular resistances in Group I and II PH, and both cytokine and molecular biomarkers of disease, but also indicated the potential for a substantial positive effect on heart function under load stress. In this Phase II project, we will establish the remaining data needed to proceed to commercialization through the following aims: 1) we will test the safety and molecular efficiency of 2-HOBA in PH patients in a small open label mechanistic pilot trial with of two weeks of 2-HOBA exposure; 2) we will demonstrate efficacy of 2HOBA in improving function of the right ventricle under stress in a well-established sheep model; and 3) we will test effectiveness of 2-HOBA alone and in the context of standard-of-care in mouse models and large animals. 2-HOBA is an entirely new approach to solving a molecular problem that several existing clinical trials and case reports have tried to resolve, but so far with limited success. The specific mechanism of action of 2-HOBA should allow it to succeed where other interventions have failed.
Topic Code
NHLBI
Solicitation Number
PA22-179
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
9/1/21
Start Date
8/31/26
End Date
Funding Split
$3.1M
Federal Obligation
$0.0
Non-Federal Obligation
$3.1M
Total Obligated
Activity Timeline
Transaction History
Modifications to R42HL158393
Additional Detail
Award ID FAIN
R42HL158393
SAI Number
R42HL158393-3085860133
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Small Business
Awarding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Funding Office
75NH00 NIH National Heart, Lung, and Blood Institute
Awardee UEI
N5NDNJL8QGA1
Awardee CAGE
7DW28
Performance District
IA-04
Senators
Charles Grassley
Joni Ernst
Joni Ernst
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,173,060 | 100% |
Modified: 8/20/25