Larazotide Acetate Reduces Intestinal Permeability in a NASH Preclinical Study

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By Jefferson Adams

December 20, 2018
By Jefferson Adams • December 20, 2018

Larazotide Acetate Reduces Intestinal Permeability in a NASH Preclinical Study

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Reviewed and edited by a celiac disease expert.

Recent data show that larazotide acetate has a marked effect on intestinal permeability. Will that lead to new treatments?

Caption: Veiled. Image: CC--ButterflySha

Celiac.com 12/20/2018 - Intestinal permeability is thought to play a key role in the translocation of bacteria that lead to nonalcoholic fatty liver disease (NAFLD), a disorder in which fat accumulates in the liver. Intestinal permeability is also thought to play a significant role in the development of Nonalcoholic steatohepatitis (NASH).

In a new preclinical study, a team of researchers affiliated with Innovate Biopharmaceuticals recently assessed the effects of larazotide acetate on intestinal permeability. Their data from that study show that larazotide has a marked effect on intestinal permeability.

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The company expects to see more data detailing the use of larazotide in combination with approved drugs liraglutide (VICTOZA®) and obeticholic acid (OCALIVA®), in development for treatment of NASH, by early 2019. Based on larazotide's ability to re-normalize intestinal permeability, the parent company plans to launch clinical development program targeted at NASH in 2019.

In the most recent study, researchers evaluated the effects of larazotide in a model of NASH that develops from consumption of a specified diet, the DIAMONDTM mouse model. The pre-clinical model confirms NAFLD/NASH in response to a high fat, high sugar Western diet, including insulin resistance, obesity, which mirrors human disease progression and histopathology.

As tested, larazotide triggered a clear reduction in gut barrier permeability, a known pathological abnormality in chronic liver diseases, specifically NASH. Any drug that can prevent or reduce gut permeability could be helpful in treating NASH. The company plans to share the complete NASH pre-clinical results for publication in 2019.

According to Dr. Arun Sanyal, Professor and Chair, Division of Gastroenterology, Hepatology and Nutrition at the Virginia Commonwealth University (VCU) School of Medicine, "Increased intestinal permeability has been linked to many aspects of metabolic syndrome including type 2 diabetes and nonalcoholic fatty liver disease. The demonstration of reduced gut permeability with larazotide in the setting of diet-induced obesity opens up the possibility of modulating the outcomes of metabolic syndrome, including NASH, via this mechanism and warrants further development for these indications."

Obviously, any drug that can reduce gut permeability could also have implications for the treatment of celiac disease. Look for celiac.com to bring you more news on efforts to develop treatments for NASH, NAFLD, and related conditions, as information becomes available.

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Guest Carol T

Posted December 25, 2018

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I have also a problem with vitamin and nutrient uptake. Will decreased permeability increase this?

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lyfan 12

Posted December 26, 2018

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Carol, they are early in research and you can expect at least five years, more likely ten, before there's anything on the market. Since "uptake" can be more complex than just leaking across the intestine, you might want to contact the researchers to see if they have/can look into this aspect while the research is still early.

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About Me

Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University. His articles, essays, poems, stories and book reviews have appeared in numerous magazines, journals, and websites, including North American Project, Antioch Review, Caliban, Mississippi Review, Slate, and more. He is the author of more than 2,500 articles on celiac disease. His university coursework includes studies in science, scientific methodology, biology, anatomy, physiology, medicine, logic, and advanced research. He previously devised health and medical content for Colgate, Dove, Pfizer, Sharecare, Walgreens, and more. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of numerous books, including "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

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