Novel Strategies to Combat Post-Traumatic Osteoarthritis (PTOA)
Abstract
This focused program project titled “Novel Strategies to Combat Post-Traumatic Osteoarthritis (PTOA)” addresses the Peer Reviewed Medical Research Program topic of “Post-Traumatic Osteoarthritis.” Our five related projects study several creative ways to slow down or even prevent arthritis from developing after joint injuries. Arthritis refers to painful and inflamed joints that limit mobility. Osteoarthritis (OA), or “wear and tear” arthritis is most common, and affects those who have served in the military more frequently and at younger ages than the general public. Injuries, to include overuse of joints, such as what might occur through running in combat boots, accelerate OA development and can result in early disability. More severe injuries such as anterior cruciate ligament tear (ACLT), a common knee injury that occurs much more frequently in teenagers, young adults, and military Service members, lead to PTOA in roughly half of patients just 10 years later. This can mean developing PTOA at a young age when most people are focused on building their families and their careers. There are currently no treatments that prevent or slow down OA progression, once it starts. Part of the reason we lack disease-modifying treatments is that patients are not aware that the cartilage that lines the joint and allows for smooth motion may be injured because they typically don’t have symptoms until the damage is irreversible, and it is too late. This is because joint cartilage does not have nerves or a blood supply. This means that cartilage also doesn’t heal well, and there is no early warning because potentially treatable small injuries don’t hurt. We have built a program of research based on several decades of previous work to offer new solutions to treat and prevent development of PTOA. Our experienced team of experts is led by a Veteran who is an orthopedic surgeon treating knee injuries at the VA Palo Alto Health Care System and at Stanford University, the affiliated academic medical center. She is a West Point graduate who formerly commanded an Imagery Intelligence unit. Through National Institutes of Health funding, she built on imaging experience gained during military service to develop new ways to color map and evaluate joint cartilage using specialized magnetic resonance images (MRI) where early cartilage damage that may actually heal can be easily seen. An esteemed mechanical engineer and a rheumatologist/immunologist on our team have also identified several new methods and types of blood tests to help provide early warning of joints at risk for PTOA. Our team has worked closely together for several years and includes a molecular biologist, several top doctors and surgeons, and a veterinary surgeon. Here is what we plan to do. When joints are injured, they bleed. The cartilage is not normally exposed to blood, and bleeding triggers inflammation that can persist to harm the joints. In Project 1, we have shown that mice do not get PTOA if we prevent “anti-clotting” activity. We will work to understand how this happens. Understanding why this works can lead to new blood tests and new treatments to prevent PTOA. In Project 2, we will use an inexpensive U.S. Food and Drug Administration-approved medicine that is already widely used during orthopedic surgery to reduce bleeding, to block “anti-clotting” activity and see if it reduces inflammation after ACLT in young patients. We will then use our new MRI methods to see if this treatment reduces cartilage damage. In Project 3, we will use the latest techniques to “rejuvenate” adult skin cells into stem cells and see if these more youthful cells can reduce inflammation and help heal cartilage after ACLT. Our MRI color maps show cartilage damage in many patients with normal looking regular MRI scans after ACL injury, who have no symptoms when we see them 1 and 2 years later. These MRI color map changes are most apparent in an area of the knee that is loa
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810590
Entities
People
- Constance Chu
Organizations
- United States Army
- VA Palo Alto Health Care System