Targeting LRH-1 to Treat Ulcerative Colitis
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that currently affects 900,000 Americans. UC is an immunological condition, characterized by chronic inflammation of the bowel. UC patients experience chronic inflammation that leads to severe ulcers, and a large number of physiological problems. Several Food and Drug Administration (FDA)-approved medications are available for IBD; however, these drugs often fail to sustain long-term disease remission due to loss of response, immunogenicity, and worsening of the disease. Each of these approved treatment strategies have significant limitations, and our goal is to develop a safe oral medication that effectively treats UC. To achieve precise control of inflammation in the gastrointestinal (GI) tract, we are developing a small molecule therapeutic that operates through a new mode of action. Here, activation of native anti-inflammatory machinery will restore intestinal health. Liver receptor homolog-1 (LRH-1) is a phospholipid-activated nuclear hormone receptor that is expressed in the intestinal epithelium, where it maintains epithelial integrity and protects against inflammatory damage through multiple mechanisms. In our preliminary studies, we have discovered that an effective small molecule LRH-1 agonist reverses inflammation and disease in a commonly used mouse model of UC. The objective of this study is to optimize our LRH-1 small molecule agonists to reduce intestinal inflammation in models of UC.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310420
Entities
People
- Eric A. Ortlund
Organizations
- Emory University
- United States Army