Larazotide Acetate
(AT-1001)

The Discovery

The Mystery in Italy

In the 1990s, Dr.

In the 1990s, Dr. Alessio Fasano was a young Italian gastroenterologist working at the University of Maryland. He was studying cholera — the devastating diarrheal disease that kills thousands in developing countries. Fasano discovered that the cholera toxin caused diarrhea by opening up the tight junctions between intestinal cells. These junctions are like seals between bricks in a wall. When cholera forced them open, fluid flooded into the gut. Then Fasano made a startling connection: in celiac disease, the body's own protein called zonulin was doing the same thing. Zonulin was opening the gut's tight junctions, letting food particles leak into the bloodstream and triggering a devastating immune response.

The Breakthrough

Building the Solution

Fasano realized that if he could block zonulin, he might be able to treat celiac disease at its r...

Fasano realized that if he could block zonulin, he might be able to treat celiac disease at its root cause. His team designed a small peptide called larazotide acetate (originally AT-1001) that could sit in the tight junctions and prevent zonulin from prying them open. Think of it like a doorstop — zonulin tries to open the door, but larazotide holds it shut. The peptide was designed to work locally in the gut without being absorbed into the bloodstream. This meant it should have very few side effects, since it never actually entered the body's circulation.

The Trials

The First Patient's Journey

Phase 1 and Phase 2 clinical trials began in the mid-2000s.

Phase 1 and Phase 2 clinical trials began in the mid-2000s. Celiac patients who accidentally ate gluten while taking larazotide experienced significantly fewer symptoms — less bloating, less abdominal pain, fewer intestinal permeability changes. The drug was remarkably safe. Patients reported almost no side effects beyond what the placebo group experienced. For millions of people who lived in constant fear of accidental gluten exposure, larazotide offered something revolutionary: a safety net. Not a cure, but protection against the damage caused by small amounts of gluten that inevitably slip into the diet.

The Crisis

The Big Test

In 2020, Innovate Biopharmaceuticals (later 9 Meters Biopharma) launched a large Phase 3 clinical...

In 2020, Innovate Biopharmaceuticals (later 9 Meters Biopharma) launched a large Phase 3 clinical trial called the GRASSROOTS study. Over 500 celiac patients at sites across the United States participated. The trial tested whether larazotide could reduce symptoms when patients were following a gluten-free diet but still experiencing problems — which describes the majority of celiac patients. The results, however, were more complex than hoped. While some symptom measures improved, the primary endpoint didn't achieve statistical significance. The company redesigned the trial protocol and continued development.

The Legacy

A New Era Begins

Today, larazotide remains the most advanced non-dietary treatment for celiac disease in clinical ...

Today, larazotide remains the most advanced non-dietary treatment for celiac disease in clinical development. No drug has ever been approved specifically for celiac disease — patients can only avoid gluten, which is nearly impossible to do perfectly. Larazotide's approach of strengthening the gut barrier represents a fundamentally new strategy. Even if it doesn't eliminate the need for a gluten-free diet, it could protect patients from the damage caused by accidental gluten exposure. Fasano's journey from studying cholera in Italy to developing a celiac treatment in America shows how discoveries in one disease can unlock solutions for another. The tight junction — once an obscure concept in cell biology — is now a major drug target.