micro-RNA29a as a Novel Therapeutic Treatment in Inflammatory Bowel Disease
Abstract
The burden of inflammatory bowel disease (IBD) is rising globally, and there are significant economic and quality of life costs for the IBD patients and for the society, with 1 in 200 individuals affected by the disease. In the U.S. military population, prevalence of IBD is estimated to be 348 cases out of 100,000 individuals. There are significant difficulties in finding a common treatment for sufferers of IBD as each person responds to therapy differently. Even with successful management therapies, many patients encounter a diminishing therapeutic response as their treatment continues, so it is critical to develop novel, diverse approaches that can be used sequentially and interchangeably to increase the quality of life for IBD sufferers. To achieve the goal of effective individualized and targeted treatments, it is crucial to have a clear understanding of the cells and molecules involved in the IBD disease progression. The gut is an area of high immunological challenge where tolerating what is inside the intestine and delivering protection against intestinal pathogens must be maintained. Lymphocytes are key players in mediating both the protective and the tolerizing responses, but their aberrant activation in IBD can also lead to intestinal inflammation. Very low-oxygen conditions develop within an inflamed, damaged bowel leading to the activation of a protective hypoxic response that activates the program of repair and healing in the inflamed intestine. Hypoxic signaling controls a class of broad-acting molecules called microRNAs. These microRNAs are powerful regulators in a wide variety of diseases, and their role in IBD has just begun to be appreciated. MicroRNAs can decrease activation of lymphocytes and restrain their disease-causing potential. The small size and portability of microRNAs make them attractive candidates for therapeutic interventions in the clinic as they can be efficiently and easily delivered to patients. We propose to study the regulation of lymphocyte function by the microRNAs that show great promise to be employed as future therapeutic agents in human IBD patients. We anticipate that microRNA therapeutics have the potential to become a major new class of drugs in the treatment of bowel inflammation. We are planning to focus on the role for miR-29, a hypoxia-regulated microRNA, in the development of colitis and in the regulation of T-lymphocyte function. The miR-29 microRNA shows promise as an injectable therapeutic agent that could have clinical applications for alleviating disease progression in IBD patients. With the help of translational medicine, we hope to take bench-top science to the bedside of patients and make new treatments available for IBD sufferers and to combat the growing incidence of IBD morbidity in military personnel and the Veteran population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310094
Entities
People
- Agnieszka Czopik
Organizations
- United States Army
- University of Texas Health Science Center at Houston