# Evaluation of a Novel Therapeutic Approach to Treat Alcoholic Lung Syndrome

> **NIH NIH R43** · XEQUEL BIO, INC. · 2020 · $252,131

## Abstract

PROJECT SUMMARY/ABSTRACT
Twenty million people abuse alcohol in the United States and 1.8 million alcoholics are hospitalized every year.
Alcoholic lung syndrome is recognized as a significant cause of morbidity and mortality amongst this large
population, with estimated deaths approaching that of alcohol induced liver cirrhosis. Alcohol abuse induces
persistent and profound oxidative stress in the lung, causing an alcohol mediated lung injury defined by
dysfunctional epithelial barriers and an exaggerated inflammatory response to acute insults. The alcoholic lung
is primed to develop acute respiratory distress syndrome (ARDS), a severe form of pulmonary edema that often
precedes respiratory failure. Alcoholics are more susceptible to the insults including pneumonia, trauma, and
sepsis, against which the alcoholic lung is predisposed to mount this pathologic hyperinflammatory response.
There are no therapies available to treat alcoholic lung syndrome and preserve pulmonary function in this
vulnerable population. Recent research suggests that targeting tight junctions in the alcoholic lung is a promising
therapeutic approach to preventing loss of epithelial barrier integrity and acute respiratory failure in critically ill
alcoholic patients. FirstString Research has developed a novel peptide, termed aCT1, that stabilizes tight
junctions, strengthens intercellular barriers, and prevents pathological inflammation. aCT1 is a peptide mimetic
of the gap junction protein Connexin43 (Cx43) C-terminus that binds ZO-1, altering interactions with its junctional
binding partners. aCT1 peptide stabilizes ZO-1 at the cell membrane, preventing tight junction degradation in
response to injury and strengthening epithelial barriers. FirstString Research has currently advanced Granexin®
gel, a topical formulation of aCT1 peptide, through three Phase 2 clinical trials for scar reduction and the
treatment of chronic wounds. These clinical results have repeatedly demonstrated the ability of aCT1 to stabilize
epithelial barriers and promote an effective epithelial response to injury, pathologies core to alcoholic lung
syndrome. Preliminary data demonstrate the ability of aCT1 to preserve lung epithelial barrier function and
improve survival in response to direct pulmonary insult in vivo. In this Phase I SBIR, we propose to determine
the efficacy of aCT1 as a treatment for alcoholic lung syndrome. We believe therapeutically targeting tight
junctions in the alcohol damaged lung will stabilize lung epithelial barriers, mitigate the pathological immune
response, and prevent development of acute respiratory failure to improve survival of alcoholic patients. Direct
targeting of intercellular junctions represents a novel approach to stabilize the air-liquid barrier and preserve lung
function in alcoholic lung syndrome. In clinically relevant two-hit models of alcoholic lung syndrome, we will test
the ability of aCT1 treatment post insult to preserve epithelial barrier integri...

## Key facts

- **NIH application ID:** 10081623
- **Project number:** 1R43HL154975-01
- **Recipient organization:** XEQUEL BIO, INC.
- **Principal Investigator:** Carissa James
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $252,131
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10081623

## Citation

> US National Institutes of Health, RePORTER application 10081623, Evaluation of a Novel Therapeutic Approach to Treat Alcoholic Lung Syndrome (1R43HL154975-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10081623. Licensed CC0.

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