Intra-Articular Injection of Alpha-2-Macroglobulin Prevents Post-Traumatic Osteoarthritis
Abstract
Background and Objective: The proposed research addresses the Post-Traumatic Osteoarthritis (PTOA) topic area. PTOA is a disease of the joint that damages the cartilage, which permits motion between the bones of the joint. In military Service personnel, knee injuries comprise almost 5% of the reported injuries, and the risk of getting knee PTOA following any injury is substantially greater in military personnel as compared to the civilian population. In a recent study of combat-injured Warriors that could not return to duty, 28% of them were disabled due to PTOA, 92% of which were the result of a combat-related injury. In all of these cases, the diagnosis of PTOA was confirmed within 2 years of injury. Not only does PTOA lower the quality of life of wounded Soldiers, the costs associated with medical care, lost duty time, and the increased likelihood of disability discharge following injury in military populations are tremendous. Traditionally, these joint injuries are surgically treated to restore biomechanical stability to the joint; however, even with our best current surgical techniques, these patients still remain at high risk for PTOA. Thus, the goal of the study is to translate a promising injectable therapy, which can be used in the field to prevent PTOA, from the research laboratory to human testing. Research Plan: Since it is known that these damage enzymes in the joint cause PTOA, the proposal is to develop an injectable therapy to minimize PTOA. It is directed at the inhibition of damaging enzymes using Alpha 2 Macroglobulin (A2M), a nature master inhibitor of these enzymes that limits inflammation. In this study, we will determine if A2M, an injectable inhibitor, in combination with mini-pig PTOA model, will provide cartilage protection in the translatable large animal model that is both clinically relevant and is known to lead to PTOA, moving this novel disease-modifying therapy closer to the clinical trial phase. Impact: To date, there are no disease-modifying treatments, other than joint replacement surgery, to stop the onset and progression of osteoarthritis for patients suffering from a joint injury. In support of the overarching challenge, the project will translate an injectable method to prevent osteoarthritis. Injectable therapy is the focus of this study since it can be administered in the field at the time of injury, which will provide the best benefit to the patient. The therapy has been shown to work in the lab and is ready for translation into clinical use. This study will enable this to happen and will result in new treatment that can change the course of PTOA. The successful translation of this therapy from the lab to human use will be critical to the reduction of pain and the improvement in the quality of life of our active military personnel, Veterans and their families. It will also benefit the civilian population at risk for PTOA and aging osteoarthritis. Military Relevance: Successful implementation of injectable therapy to restore articular cartilage health after joint injury and prevent PTOA has the potential to significantly improve the quality of life for thousands of wounded Warriors and to maximize their function for return to duty or civilian life. The therapy under study could be administered in the field at the time of injury to prevent post-injury arthritis onset, or later in the clinic to stop post-injury arthritis progression.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910516
Entities
People
- Lei Wei
Organizations
- Rhode Island Hospital
- United States Army