# 2-HOBA for Treatment of Pulmonary Hypertension

> **NIH NIH R41** · MTI BIOTECH, INC. · 2021 · $256,580

## 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 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.

## Key facts

- **NIH application ID:** 10257863
- **Project number:** 1R41HL158393-01
- **Recipient organization:** MTI BIOTECH, INC.
- **Principal Investigator:** John A Rathmacher
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $256,580
- **Award type:** 1
- **Project period:** 2021-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10257863

## Citation

> US National Institutes of Health, RePORTER application 10257863, 2-HOBA for Treatment of Pulmonary Hypertension (1R41HL158393-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10257863. Licensed CC0.

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