A New Treatment for Acute Pancreatitis Injury and Pain
Abstract
The proposed research project addresses the Fiscal Year 2022 Peer Reviewed Medical Research Program Topic Area of Pancreatitis and will pursue the Strategic Goal of establishing a new Treatment. Our overarching goal is to develop a novel new treatment that effectively decreases the pain and severity of acute pancreatitis. This disease is not uncommon in our Armed Forces populations and has become over 25% more common over the past 15 years. It is most often caused by cigarette smoking, alcohol abuse, and gallstones. There is often prominent morbidity in those with severe acute pancreatitis; mortality occurs in up to 25%—long-term complications including diabetes and an increased risk for pancreatic cancer. One of the hallmarks of this disease and one of its three diagnostic criteria is severe debilitating abdominal pain. There are no specific treatments for acute pancreatitis, and therapy is primarily limited to intravenous fluids. The most frequently used pain medications are opiates, but they often cause unwanted side effects such as nausea and vomiting, can worsen pancreatitis, and carry a risk of opiate addiction. An ideal therapy for acute pancreatitis would decrease disease severity and reduce the associated pain and not be an opiate. Our preliminary and published work suggests that renalase, a protein found in blood, may have such properties. We have shown that the whole renalase protein has potent anti-inflammatory and prosurvival properties and that it dramatically reduces injury in several preclinical (mouse) models, including acute pancreatitis. Such models are used to determine whether a treatment has the potential to work in humans. We found renalase s anti-inflammatory and survival effects in a renalase peptide that we developed into a drug. Our preliminary data shows the drug dramatically reduces pancreatic injury and pain in mice with severe pancreatitis. The reduced pain responses are seen in intact animals and nerves. We propose to use several mouse models of severe acute pancreatitis to understand whether the treatment could help treat acute pancreatitis injury caused by different etiologies. We will also examine if it can be effective if given before or after disease onset and assess its ability to reduce pain-related responses in whole animals using clinically relevant animal models in vivo and nerves isolated from those animals in vitro. If our hypothesis is proven and subsequent findings in human studies show similar results, the treatments have the potential to reduce acute morbidity and mortality from this disease. By not activating opiate pathways, it avoids the risk of opioid addiction. Furthermore, by decreasing the initial severity of acute pancreatitis, the therapy could reduce its long-term complications such as diabetes and pancreatitis cancer and reduce the otherwise added significant healthcare costs. This renalase-agonist and the scientific understanding pursuant to the proposed studies potential to reduce the impact of acute pancreatitis, an unpredictable disease, on the readiness of our Armed Forces and to improve the health of those in service, their dependents, and the citizens of the United States.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310329
Entities
People
- Fred S. Gorelick
Organizations
- United States Army
- Yale University