Development of Diagnostic and Treatment Strategies for Post-Traumatic Osteoarthritis (PTOA)
Abstract
Post-traumatic osteoarthritis (PTOA) is the primary source of disability in Warriors. Among Warriors diagnosed with PTOA, 94% are attributed to combat injury. Some of the most common causes are secondary to explosions, traumatic open joint wounds, fragment projectiles, and gunshot wounds. To date, no effective therapies have been developed for PTOA in military recruits in the Army, Marines, and Air Force Services, which have been found to be significantly at-risk populations that will develop debilitating joint disease. PTOA is still principally diagnosed radiographically, frequently after irreversible tissue damage has occurred, and no reliable biomarker assays have been able to definitively define the disease and allow adequate diagnosis or response to therapies. A potentially promising therapy involves blocking inflammation using gene therapy by inhibiting the primary receptor of inflammation in the joint, IL-1ß receptor, using a therapy, IL-1ra. Additionally, enhancing joint health through gene-therapy-based delivery of growth molecules, such as insulin-like growth factor (IGFI), promotes cartilage healing by up-regulation of the building blocks of cartilage, specifically collagen and proteoglycans. Further, identification of reliable biomarkers that accurately represent the stage and progression of PTOA so that earlier detection could be accomplished, as well as the extent of response to therapy, remains challenging. This proposal addresses the focus area of osteoarthritis (OA), specifically improving the outcomes of those who suffer from PTOA. The intent of the award is to investigate a treatment strategy involving large animal studies to improve outcomes and diagnoses of OA and/or PTOA. The proposed research will impact the important focus area of OA and PTOA by discovering a long-term therapy that will be able to prevent progression of military personnel and their families that suffer from PTOA and OA. Further, it will result in a diagnostic strategy, through biomarkers and imaging, to identify people who are at risk of developing PTOA and verify those who are or are not responding to treatment. The clinical applications of this therapy are that its optimization in an animal model will lead to a clinical trial in people that will lead to effective treatment of PTOA, as well as prevention of progression of the leading cause of arthritis in military personnel and their families and caretakers. By establishing a reliable profile of biomarkers in this proposal to detect this disease’s onset, progression, and prevention, clinicians will be able to identify at-risk Warriors and utilize the treatment developed in this proposal. The benefits would be the ability, for the first time, to effectively diagnose and treat PTOA for the millions of military and ex-military personnel and their families and caretakers. The risks include an extended timeline to reach this goal; however, with the team of experts included in this proposal and the expansive amount of promising preliminary data, combined with the many Food and Drug Administration (FDA) trials currently being approved, the Principal Investigator and the coinvestigators believe this risk to be minimal. The team involved with this proposal project believes the timeline to achieve the expected patient-related outcomes to be approximately 2-3 years following completion of this translational work. The members of this team consist of individuals that have carried out important large animal translational studies; an M.D. (who is also a Veteran) that specializes in joint disease and is currently carrying out several clinical trials in new orthobiological therapies, specifically in a hospital that is treating military personnel and Veterans; and a gene therapist that has over 25 years’ experience in developing gene therapeutics and instituting them in clinical trials that are recognized and sanctioned by the FDA.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 03, 2019
- Source ID
- W81XWH1810572
Entities
People
- Laurie Goodrich
Organizations
- Colorado State University
- United States Army