Intestine-targeted LXR therapy to protect the liver in short gut syndrome
Official title: Intestinally restricted LXR agonism in ameliorating liver failure in short gut syndrome
Funded at Washington University · NIH-11370663 · Data updated 2026-11-12
This project will try an intestine-only drug that activates LXR to help children with short gut syndrome avoid liver damage.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project start | March 1, 2019 |
| Project end | February 28, 2029 |
| Funding year | 2026 |
| Award (this year) | $590,587 |
| NIH project number | 5R01DK119147-08 |
| Project ID | NIH-11370663 on NIH RePORTER |
Who could benefit from this research
✓Could help
Children (infants through about 11 years old) who have had major small intestine resection and are living with short gut syndrome or are at risk for intestinal failure-associated liver disease.
✕Less likely to help
People without short gut syndrome or whose liver disease is caused by unrelated conditions (for example genetic liver diseases) are unlikely to benefit from this intestine-focused approach.
What this research studies
From a patient's perspective, researchers are testing a drug that works only in the intestine to boost protective HDL made by gut cells and block harmful gut bacteria products from reaching the liver. In lab models of bowel resection they give the intestine-targeted LXR agonist and measure liver inflammation, fibrosis, and gut HDL production tied to ABCA1 and apoA1. They study how gut-derived HDL neutralizes LPS and prevents TLR4-driven liver injury after short bowel surgery. The work aims to show whether strengthening this gut-to-liver defense can prevent intestinal failure-associated liver disease after major small intestine loss.
Why it matters
Potential benefit: If successful, this approach could lower the chance of liver failure and reduce the need for long-term parenteral nutrition in children with short gut syndrome.
How similar studies have gone: Prior preclinical mouse work from the investigators suggests gut-derived HDL can neutralize LPS and limit liver fibrosis, but intestine-restricted LXR therapy has not yet been tested in people.
Where this research is happening
-
Washington University
Saint Louis, United States Active
Researchers
- Principal investigator: Randolph, Gwendalyn J — Washington University
- Study coordinator: Randolph, Gwendalyn J
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.