New Strategies in Targeted Interventions for Posttraumatic Osteoarthritis (PT-OA)
Abstract
This project addresses "post-traumatic osteoarthritis" (PT-OA), which has been identified as an area of priority research by the Department of Defense. This project is directly relevant to specific knowledge gaps and research priorities also identified by the Department of Defense, which are to develop preventive therapies to minimize PT-OA progression after traumatic injury to the joint and to develop therapies to treat disease via sustained release of agents that can be directly and non-invasively injected into the joints. Individuals who sustain traumatic injury to their joints are at risk for developing PT-OA, which is a form of osteoarthritis (OA) with particularly rapid onset that leads to painful and disabling disease in otherwise healthy and relatively young adults. As PT-OA afflicts people during their most active years, strategies for clinical therapies that delay PT-OA progression are urgently needed to maintain the quality of life of these individuals. PT-OA is a major factor accounting for the increased rates of OA in the US military. A major cause of PT-OA in the military is battlefield trauma. Thus, it is particularly important for military members who have suffered combat- or service-related joint trauma, who consequently are high risk for PT-OA, to have a treatment available that can slow the progression of cartilage damage and resulting disability in order to facilitate their return to active duty. We propose that the key to prevention and treatment of PT-OA is to develop interventions that target the distinct responses that occur in the injured joint at different phases of disease. Specifically, this project will investigate a novel therapeutic approach for PT-OA in which potential therapeutic agents will be directly delivered into the joint at different times in disease progression in order to target the distinct responses that occur at different phases of disease. We hypothesize that stimulating beneficial responses, and inhibiting harmful ones, will slow the onset and progression of PT-OA following traumatic joint injury. This research establishes a new model for PT-OA disease that centers on the distinct responses in the injured joint, which will be exploited to develop novel interventions for PT-OA that will augment beneficial responses to injury in the joint while inhibiting harmful responses. This research will benefit all individuals at risk for PT-OA, especially military Service members who have sustained traumatic joint injuries. A near-term benefit of this research will be to advance our novel therapeutic concept into preclinical studies in large animal models, as a next step prior to clinical trials and to lay the foundation for future mechanistic studies that may reveal additional new disease targets. The impact of the project is to provide near-term, clinically relevant proof-of-concept that our approach offers a new mechanistically based therapeutic intervention for PT-OA.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510144
Entities
People
- Caroline N. Dealy
Organizations
- United States Army
- University of Connecticut Health Center