# Pre-clinical Validation of A Novel Protein Drug Candidate for ASH and NASH Treatment

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2022 · $614,398

## Abstract

Summary
Alcoholic Steatohepatitis (ASH) and Nonalcoholic Steatohepatitis (NASH) affects a large
population in US and worldwide. Currently, major unmet medical needs include lack of method or
agent to specifically deplete activated HSC and capillarized LSEC as well as noninvasive
methodology and reagents to visualize collagen build-up, HSC activation, and LSEC
capillarization in fibrotic liver. We have developed a protein drug candidate (referred to as
“ProAgio”) that targets integrin αvβ3 at a novel site to induce apoptosis of integrin αvβ3 expressing
cells by a novel mechanism. ProAgio specifically induces apoptosis of integrin v3 expressing
cells with a high efficacy by recruiting & activating caspase 8 at cytoplasmic domain of. We
demonstrated in our preliminary studies that treatment of mice that carries liver fibrosis/cirrhosis
induced by TAA/alcohol CCl4 and the high-fat diet induce NASH mice with ProAgio reversed liver
fibrosis/cirrhosis. In addition, we have developed novel protein MRI contrast agents (ProCAs) that
allow us to assess collagen contents and integrin αvβ3 positive HSCs & LSECs in fibrotic liver.
MR imaging of fibrotic mice demonstrated superior properties of our developed contrast agents
for collagen and integrin v3 positive cell assessment. Preliminary toxicity analyses with healthy
mice indicate that ProAgio and our developed MRI contrast agents are not toxic to mice at very
high dose. The goal of this project is to vigorously pre-clinical validation of ProAgio as a drug
candidate for ASH/NASH patient treatment. We will achieve our objective by three specific aims.
Aim 1 is to examine the effectiveness of ProAgio in reversal of liver fibrosis using high-fat diet
plus multiple binge alcohol and chronic alcohol binge induced ASH models. Investigation of the
effects of ProAgio in ASH mouse models will further pre-clinical validation of ProAgio as an
ASH/NASH treatment drug. Aim 2 is to monitor and validate the effects of ProAgio on collagen
and HSC in fibrotic liver by MR imaging using our developed MRI contrast agents. Our MR
imaging aided validation will not only validate the effectiveness of ProAgio as an ASH/NASH
treatment agent, but also validate the target and mechanism of drug action. Aim 3 is Pre-clinical
validations of ProAgio as an ASH/NASH treatment drug candidate via toxicology (TOX) and
pharmacokinetic (PK) analyses. Our study will open a new avenue for ASH/NASH treatment and
diagnosis/prognosis by protein design. Success in our studies will not only develop a new protein
drug for liver fibrosis/cirrhosis treatment but also test highly effective MRI contrast agents that
allow us to accurately and non-invasively monitor fibrosis progression and regression for
assessment of treatment effects. Such development is expected to fill in the major medical gaps
and to facilitate to devise treatment strategy to reverse fibrosis and follow high risk patients.

## Key facts

- **NIH application ID:** 10476313
- **Project number:** 5R01DK126080-02
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Jenny J. Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $614,398
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476313

## Citation

> US National Institutes of Health, RePORTER application 10476313, Pre-clinical Validation of A Novel Protein Drug Candidate for ASH and NASH Treatment (5R01DK126080-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10476313. Licensed CC0.

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