Larazotide acetate: a pharmacological peptide approach to tight junction regulation

Larazotide acetate (LA) is a single-chain peptide of eight amino acids that acts as a tight junction regulator to restore intestinal barrier function. LA is currently being studied in phase III clinical trials and is orally administered to adult patients with celiac disease as an adjunct therapeutic...

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Published inAmerican journal of physiology: Gastrointestinal and liver physiology Vol. 320; no. 6; pp. G983 - G989
Main Authors Slifer, Zachary M, Krishnan, B Radha, Madan, Jay, Blikslager, Anthony T
Format Journal Article
LanguageEnglish
Published United States American Physiological Society 01.06.2021
Subjects
Acetic acid
Actin
Animals
Arthritis
Celiac disease
Celiac Disease - drug therapy
Celiac Disease - metabolism
Clinical trials
Collagen
Filaments
Gliadin
Humans
Intestine
Ischemia
Kinases
Myosin
Myosin-light-chain kinase
Oligopeptides - pharmacology
Oligopeptides - therapeutic use
Oral administration
Peptides
Permeability
Recovery of function
Tight Junction Proteins - metabolism
Tight Junctions - drug effects
Tight Junctions - metabolism
celiac disease
barrier function
tight junction
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Summary:Larazotide acetate (LA) is a single-chain peptide of eight amino acids that acts as a tight junction regulator to restore intestinal barrier function. LA is currently being studied in phase III clinical trials and is orally administered to adult patients with celiac disease as an adjunct therapeutic to enhance intestinal barrier function that has been disrupted by gliadin-induced immune reactivity. Mechanistically, LA is thought to act as a zonulin antagonist to reduce zonulin-induced increases in barrier permeability and has been associated with the redistribution and rearrangement of tight junction proteins and actin filaments to restore intestinal barrier function. More recently, LA has been linked to inhibition of myosin light chain kinase, which likely reduces tension on actin filaments, thereby facilitating tight junction closure. Small (rodent) and large (porcine) animal studies have been conducted that demonstrate the importance of LA as a tight junction regulatory peptide in conditions other than celiac disease, including collagen-induced arthritis in mice and intestinal ischemic injury in pigs.
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ISSN:0193-1857
1522-1547
DOI:10.1152/AJPGI.00386.2020