# Oral elafin formulation for intestinal fibrosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $359,522

## Abstract

Project Summary
Prolonged Crohn’s disease leads to intestinal fibrosis, which is difficult to prevent or treat. The surgical
resection may negatively impact a patient’s quality of life. Thus, new therapeutic approaches are
actively sought after. We have recently shown that intestinal expression of antimicrobial peptide and
protease inhibitor elafin is reduced in stricturing CD patients. Its potential protective effect in intestinal
fibrosis has never been reported in the literature. Our preliminary data showed that elafin-
overexpression inhibited preexisting colonic fibrosis in TNBS-mediated mice, Salmonella-infected
mice, and SAMP1/YitFc mice. We generated an orally active elafin-Eudragit formulation for potential
therapeutic applications. The elafin-Eudragit formulation reversed preexisting colonic fibrosis in
TNBS-treated mice. We also discovered that elafin inhibits collagen expression in the intestinal
fibroblasts by modulating several stricture-specific genes. We hypothesize that oral administration of
modified elafin may be useful for treating colitis-associated intestinal fibrosis by affecting a stricture-
specific pathway. We propose to (1) establish oral therapeutic regimens of modified elafin for treating
intestinal fibrosis in a mouse model of preexisting intestinal fibrosis and (2) determine the cathepsin S-
PAR2-miR205-ZEB1-mediated anti-fibrogenic mechanism of elafin in intestinal fibroblasts. The overall
impact of this study will produce a comprehensive assessment of optimized oral elafin delivery
approaches for intestinal fibrosis. This mechanistic study will reveal how and why elafin inhibits
intestinal fibrosis.

## Key facts

- **NIH application ID:** 10597557
- **Project number:** 5R01DK128142-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Hon Wai Koon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $359,522
- **Award type:** 5
- **Project period:** 2022-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10597557

## Citation

> US National Institutes of Health, RePORTER application 10597557, Oral elafin formulation for intestinal fibrosis (5R01DK128142-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10597557. Licensed CC0.

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