Science

Science

GI Science Explained

The intestinal barrier forms the protective inner lining of the intestinal tract.

Intestinal Villi
A variety of events can cause the breakdown of the intestinal barrier, including:
  • 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).
Doctors in operating room

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.
Digestive enzymes from a compromised intestinal barrier can cause a range of complications
When the intestinal barrier is compromised, digestive enzymes can leak into the lumen, causing a range of complications, including:
  • 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.
  • 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. Adhesions may result in hospital readmissions due to pain or bowel obstructions. Additionally, adhesions may lead to infertility and can complicate future abdominal surgeries.

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. In multiple clinical studies, a single dose of LB1148 prior to gastrointestinal surgery has demonstrated positive results in accelerating the time to return of postoperative bowel function and preventing the post-surgical formation of abdominal adhesions.

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.