Potential Therapeutic Use of Relaxin in Healing Cranial Bone Defects
Abstract
Critical Problem: US Military involvement in Operation Enduring Freedom/Operation Iraqi Freedom and other recent conflicts has resulted in thousands of head, jaw and facial bone fractures in front-line active duty Service members. The occurrence of these injuries is expected to rise in future conflicts partly because of the increasing use of improvised explosive devices by adversaries. Even those military personnel not in front-line combat positions are at risk for this kind of injury due to on-the-job motor-vehicle accidents. Unfortunately, failed or delayed bone healing represents a major clinical problem. An important limiting factor in bone healing is the reduced amount of blood flow to the fractured bone, because the blood vessels are broken or disrupted by the trauma. In addition, blood flow to the bone may already be compromised in Soldiers who smoke or have high cholesterol as these conditions are associated with blood vessel disease. Therefore, therapeutic agents are needed, which will improve bone blood flow and healing of head, jaw, and facial bone fractures. Innovative Solution: One approach to speeding up the healing of fractured bone in the head, jaw, and facial region would be to administer a therapeutic agent that would increase blood flow to the injured bone. Specifically, we want this agent to facilitate sprouting of new blood vessels from existing blood vessels at the fracture site, thus replacing the broken ones and restoring blood flow. In addition, we want this therapeutic agent to increase blood vessel precursor cells in the bloodstream that come from the bone marrow, so that they can go to the injury site and form brand new blood vessels. Further, we want this new treatment to directly enhance blood flow to the bone by causing dilation of the surviving (uninjured) and newly forming blood vessels that, in turn, leads to increased blood flow. Finally, we want this therapeutic agent to directly stimulate bone formation, and to be safe with minimal or no harmful side effects. To date, we are unaware of a single Food and Drug Administration-approved agent that has all of these beneficial characteristics. However, the hormone "relaxin" meets all of these criteria and provides an innovative approach to hasten head, jaw, and facial fracture healing. Relaxin is a naturally occurring hormone in women that comes from the ovary circulating in the late menstrual cycle and during pregnancy. Though it is unlikely to circulate in men, administered relaxin is also biologically active in males because relaxin and its receptor are made in blood vessels and other tissues in both men and women where relaxin exerts a local effect. Applicability: We envision that if our proposed studies are successful in demonstrating relaxin s ability to accelerate healing of a head bone fracture in our (preclinical) animal model, then this positive outcome would pave the way for clinical trials in humans designed to test efficacy and safety. It is important to underscore that relaxin has already been shown to have a safe profile in clinical trials for pathologies unrelated to bone fracture, making this newly proposed application, if our animal studies go well, that much closer to clinical reality. Impact: In this Discovery Award proposal, we propose the novel application of relaxin to improve healing of head, jaw, and facial fractures. Relaxin has numerous biological effects, many of which are likely to benefit bone fracture healing, and it has an excellent safety profile in humans. This new approach that we propose has not been previously thought of or attempted and, if successful, will have a major impact on advancing relaxin towards clinical trials focused on shortening the time needed for healing of head, jaw, and facial fractures in our active duty military personnel.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510162
Entities
People
- Kirk P Conrad
Organizations
- United States Army
- University of Florida