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.
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.
Partnership with The University of California
In partnership with The University of California, we have decades of groundbreaking scientific research highlighting the importance of intestinal integrity and the medical complications that can occur when the intestinal epithelial barrier is disrupted. That’s why we’re focused on the role of intestinal barrier biology in human disease and designing targeted therapeutics to provide solutions for patients and physicians.
A Worldwide Exclusive License to Patent Rights
To pursue the latest science and offer patients new options for fighting chronic disease, we entered an exclusive license with the Regents of the University of California (UC) to expand our proprietary technology for detecting enzymatic protease activity in human clinical samples. Under the terms of this agreement, in combination with a related 2020 license from UC, Palisade Bio has worldwide exclusive license to patent rights covering certain engineered substrates and use in measuring degradative enzymes for disease conditions, including cancer. This technology was originally developed in the laboratory of Dr. Michael Heller at the University of California San Diego.
A Deep Understanding of Intestinal Barrier Biology
We leverage a tested, patented approach to understanding intestinal barrier biology and data-driven research. Tapping into this understanding, and with our worldwide exclusive license, we are expanding our proprietary whole-blood assay to identify the specific protease activity contributing to human disease. As we build our pipeline of drug products, these assets create platforms for novel targets and drug discovery, as well as highly efficient patient selection and measurement of clinical response during drug development.