# The treatment of Alcohol Liver Disease with Retinoid Beta Agonists

> **NIH NIH SC2** · HUNTER COLLEGE · 2020 · $156,000

## Abstract

Project Summary/Abstract
Alcoholic liver disease (ALD) is responsible for more than half of all liver-related deaths in the United
States. ALD and defined as a spectrum of disorders that begins with steatosis (fatty liver), that can
progress to steatohepatitis, cirrhosis, and fibrotic end stage liver disease (ESLD). Current treatment
options are focused on behavioral and pharmacological approaches for eliminating alcohol
consumption and cravings. Individuals that struggle with alcohol abstinence face a higher risk of
developing ALD cirrhosis, thus there is an urgent need for novel anti-ALD therapies. There is
convincing evidence that the progression of ALD is driven by reductions and dysregulation of
hepatic vitamin A (VA, retinol) metabolism and pathways. VA and related molecules are collectively
called retinoids, which, acting through the VA metabolite retinoic acid (RA), and RA receptors (RAR
α, β and γ), regulate the expression of genes involved in lipid metabolism, inflammation and anti-
fibrotic pathways implicated in the development of ALD. I hypothesize that synthetic agonists for
specific RARs, some of which are FDA approved for the treatment of some cancers, can activate and
restore hepatic VA signaling pathways and have high therapeutic potential. I have generated
preliminary data demonstrating that the specific RARβ2 agonist; AC261066, can significantly reduce
hepatic steatosis, production of reactive oxygen species (ROS), and activation of scar forming hepatic
stellate cells (HSCs) in a model of dietary induced non-alcoholic fatty liver disease (NAFLD). ALD
and NAFLD share several clinical and molecular features, therefore this project will propose to
determine i) the effectiveness of RARβ2 agonists on preventing HSC and liver fibrosis in a short-
term, murine model of moderate alcohol intake, and ii) the therapeutic efficacy of RARβ2 agonists on
reversing the clinical hallmarks of chronic alcohol abuse using the National Institute on Alcohol Abuse
and Alcoholism (NIAAA) murine model of chronic, binge alcohol liver injury. This project proposes
an innovative approach to the development of ALD therapies by using agonists for RARβ which
possesses similar anti-fibrotic properties of RA but, unlike RA, are not susceptible to ethanol-driven
catabolism in ALD. Data from this proposal could lead to the development of RARβ agonists as
therapies for ALD and other fibrotic liver disorders in humans.

## Key facts

- **NIH application ID:** 9896840
- **Project number:** 5SC2GM127206-03
- **Recipient organization:** HUNTER COLLEGE
- **Principal Investigator:** Steven Trasino
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $156,000
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896840

## Citation

> US National Institutes of Health, RePORTER application 9896840, The treatment of Alcohol Liver Disease with Retinoid Beta Agonists (5SC2GM127206-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9896840. Licensed CC0.

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