IU Team Finds Hidden Blood Mutations Behind Severe IBD

New research suggests a drug targeting age-related blood condition could reduce inflammatory bowel disease severity.

Mar. 10, 2026 at 3:54am

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Indiana University School of Medicine scientists have uncovered new evidence that an age-related blood condition called clonal hematopoiesis of indeterminate potential (CHIP) may contribute to inflammatory bowel disease (IBD). Their findings suggest that a new drug strategy targeting CHIP may reduce IBD severity and offers a new path for treating chronic diseases like Crohn's disease and ulcerative colitis.

Why it matters

IBD is a chronic and debilitating condition that affects millions of Americans, with prevalence highest in adults 45 and older. This research identifies a new therapeutic target at the intersection of aging, blood biology, and chronic inflammation, which could lead to more effective treatments for IBD and potentially other age-related diseases.

The details

The researchers found that people with CHIP, especially those with DNMT3A gene mutations, face a significantly higher risk of developing Crohn's disease. Younger individuals with large TET2 gene mutations also had an increased risk of ulcerative colitis. In mouse models, blood stem cells carrying CHIP mutations led to more severe tissue damage and immune-cell buildup in the colon. The scientists identified the APE1/Ref-1 inflammation pathway as a key driver and showed that using a drug called APX3330 to block that pathway reduced inflammation and restored colon health.

  • The research was recently published in the journal Blood.
  • The IU team is now preparing for a Phase Ib clinical trial to test APX3330 in human IBD patients.

The players

Reuben Kapur

PhD, director of the Herman B Wells Center for Pediatric Research and co-author on the study.

Ramesh Kumar

PhD, assistant research professor of pediatrics at the IU School of Medicine and lead author of the study.

Mark Kelley

PhD, IU scientist who developed the drug APX3330.

Indiana University School of Medicine

The largest medical school in the U.S. and annually ranked among the top medical schools in the nation by U.S. News & World Report.

Centers for Disease Control

Estimates that 2.4 to 3.1 million people have IBD in the United States.

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What they’re saying

“Our research identifies a new therapeutic target that sits at the intersection of aging, blood biology and chronic inflammation. We found that these mutant blood cells in CHIP 'supercharge' inflammation in the gut, but more importantly, we discovered that targeting this pathway dramatically reduced damage and normalized how the immune system behaves.”

— Reuben Kapur, PhD, director of the Herman B Wells Center for Pediatric Research and co-author on the study

“Our most exciting discovery was that a single, oral drug that's already known to be safe in humans could reverse nearly all of the harmful effects of CHIP-driven inflammation. This also suggests that even though CHIP mutations are age-related and previously thought to be untreatable, their harmful effects on inflammation may actually be reversible.”

— Ramesh Kumar, PhD, assistant research professor of pediatrics at the IU School of Medicine and lead author of the study

What’s next

The research team is now preparing for a Phase Ib clinical trial to test APX3330 in human IBD patients. They also plan to explore whether the drug could help reduce inflammation in other age-related conditions such as heart and kidney disease.

The takeaway

This research identifies a promising new therapeutic target and drug strategy for treating inflammatory bowel disease, a chronic and debilitating condition that affects millions. If successful, this approach could also have implications for reducing inflammation in other age-related diseases.