Improving nutrient absorption in microvillus inclusion disease from MYO5B mutations
Impacting the pathophysiology of malabsorption induced by Myosin Vb inactivating mutations
A drug-like compound that activates LPA receptors aims to help infants and children with microvillus inclusion disease caused by MYO5B mutations absorb nutrients and fluids more effectively.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Vanderbilt University Medical Center NIH-funded |
| Lab location | 1 site (Nashville, United States) |
| Project ID | NIH-11158695 on NIH RePORTER |
What this research studies
Researchers are developing synthetic compounds that turn on specific lysophosphatidic acid (LPA) receptors to encourage intestinal cells to mature and place absorption proteins in the right spot on the gut surface. They are testing these LPAR1 and LPAR5 activators in mouse models, in lab-grown intestinal organoids, and in patient tissue samples to see whether the drugs restore normal brush border function. Early lab work showed natural LPA can fix some cell-level defects but is poorly absorbed when given systemically, so the team made more stable, selective agonists that appear to improve intestinal structure and transporter placement in animal models. The research is being led at Vanderbilt University Medical Center and is working toward approaches that could eventually be given to patients.
Who could benefit from this research
Good fit: Infants and children diagnosed with microvillus inclusion disease due to MYO5B inactivating mutations and experiencing severe diarrhea and malabsorption would be the primary candidates.
Not a fit: People whose intestinal problems are caused by other diseases, who do not carry MYO5B mutations, or who have irreversible intestinal failure are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this approach could reduce life-threatening diarrhea and malabsorption, helping affected children gain weight and potentially decreasing reliance on intravenous nutrition.
How similar studies have performed: Laboratory studies showed natural LPA improved cell and organoid defects, and a new LPAR5 agonist improved intestinal structure in mice, but benefits in humans remain unproven.
Where this research is happening
Nashville, United States
- Vanderbilt University Medical Center — Nashville, United States (Active)
Researchers
- Principal investigator: Kaji, Izumi — Vanderbilt University Medical Center
- Study coordinator: Kaji, Izumi
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 below.