Science
Science
GI Science Explained
The intestinal barrier forms the protective inner lining of the intestinal tract.
- Physical injuries resulting from incisions and mechanical manipulations during abdominal surgery.
- Metabolic injuries resulting from prolonged low blood flow (hypoperfusion) during cardiovascular (CV) surgery.
- Damage resulting from the body’s natural response to life-threatening infections, shock and sepsis.
- Chronic inflammatory diseases, including inflammatory bowel disease (IBD).
Two common types of surgery often lead to disruption of the intestinal barrier:
- During GI and abdominal surgeries, surgeons handle, manipulate and often make incisions in the intestines.
- During cardiovascular surgery, the surgeon may have to divert blood flow through a cardiopulmonary bypass pump resulting in low blood flow to the intestines which can lead to intestinal barrier damage.
- Abdominal Adhesion: Postsurgical adhesions are scar tissue formations caused by proteolytic damage to the cells that line the exterior surface of the intestinal tract and abdominal wall. During the healing process, the body forms scar tissue that binds tissues not normally connected. The adhesions prevent normal movement and function of the intestines. Studies have shown that adhesions are responsible for 1 in 4 open abdominal surgery patients being readmitted to the hospital within 5 years due to adhesion complications (Krielen et al. 2020). Additionally, adhesions may lead to infertility and can complicate future abdominal surgeries.
- Delayed Return of Post-Operative Bowel Function: Local nerve and muscle damage and inflammation resulting in loss of bowel motility can lead to delayed return of normal bowel function. These complications may increase bowel recovery time, extending the patient’s hospitalization.
Technology
Active digestive enzymes are normally found in the small intestine where they digest food. If these enzymes become active outside the intestines, they start “digesting” healthy tissue, a process called autodigestion.
Autodigestion may lead to complications such as adhesions (scar tissue that binds organs and tissues that are not usually connected), proteolytic cleavage of cell membrane receptors leading to impaired cellular function, and chronic inflammation.
Our lead asset, LB1148, is a broad-spectrum serine protease inhibitor which acts to neutralize digestive enzymes, potentially reducing intestinal damage. LB1148 is being investigated in a Phase 2 study to evaluate its effects on intra-abdominal adhesions and return of gastrointestinal function in subjects undergoing elective bowel resection.
Our Innovation Story
Disruption in the integrity of the gastrointestinal barrier can have a cascade effect on GI health, as well as lead to the onset of oncologic, metabolic, cardiovascular, and neurological diseases. Our innovative track record has empowered us to change the future of GI surgery and treat the multitude of serious diseases caused by disruption of intestinal integrity.