Assessing an SRC Kinase Recruitment Inhibitor for Therapeutic Management of Knee Arthrofibrosis
Abstract
Focus Areas: Retention Strategies and Return to Duty Orthopedic extremity trauma is a major problem for military Service Members, resulting in limited duty days for Service Members and long-term functional disability and substantial medical cost. The most common reported complication of the complex knee injury is arthrofibrosis (arthron, from Greek, meaning articulation, joint). Arthrofibrosis is an inflammatory condition that leads to the production of excessive scar tissue in or around major joints. These joints can include the knee, shoulder, ankle, wrist, and hip. Arthrofibrosis can be the result of surgery or the initial injury to the joint. The knee is the most commonly injured joint, and due to its complex anatomy, restoration of its function after complex injury represents a significant challenge. In active military members, joint injury has severe forms including multiligamentous complex knee injuries and knee dislocations caused by high-energy trauma. Return to duty after treatment of a complex knee injury in the military population is challenging, with nearly half of the injured Soldiers eventually undergoing medical discharge for their injury. Currently, no efficient treatment of arthrofibrosis is available to prevent this debilitating condition. The excess scar tissue limits range of motion, functionality, and can be painful and debilitating. Specialized care is required in the treatment of arthrofibrosis, and only a handful of orthopedic surgeons in the world have a significant amount of experience treating this condition. The rate of arthrofibrosis oftentimes triples when patients have undergone previous surgeries for multiple ligamentous injuries that require early immobilization. A number of medical, social, and genetic risk factors for developing arthrofibrosis have been identified: Patients with autoimmune diseases (e.g., lupus), patients who need total joint replacement as a result of severe and/or early onset of osteoarthritis, patients who are prone to post-operative infections or have bleeding disorders (e.g., hemophilia, platelet disorders). Arthroscopic lysis of scar tissue and manipulation under anesthesia are the most commonly performed treatments for arthrofibrosis. However, there are no guarantees of improved function or decreased pain following these approaches. In addition, both treatments damage the surrounding tissue, which may induce an inflammatory response that may cause further deposition of scar tissue, and the pharmacologic treatment for arthrofibrosis is currently limited. Administration of different anti-inflammatory drugs and biologics has been unsuccessful and there has been no specific pharmacological therapy able to prevent or cure arthrofibrosis. Thus, preventive treatment of knee arthrofibrosis after major knee injury is an unmet medical need, especially in military medicine. The proposed project is designed to advance a safe, noninvasive treatment for prevention and treatment of arthrofibrosis in high-risk groups after injury by developing a novel, highly selective, and potent small-molecule SRi-1 designed to disrupt a recruitment and signaling of a critical protein required for transferring scar-promoting signals within the specialized cells. This project will be conducted by a multidisciplinary team of surgeons, scientists, and bioengineers. Proposed studies include production and testing of slow drug-release formulations of SRi-1 using clinically approved biomaterials. The drug will be tested in a highly reproducible rodent model of posttraumatic arthrofibrosis recently developed by the research team. The development of a novel small molecule will serve as an excellent therapeutic strategy that will prevent or halt the progression of arthrofibrosis by preventing the rapid formation of scar tissue, without adversely affecting the overall wound healing process. This therapy will be especially valuable in patients from high-risk groups of i
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310718
Entities
People
- Denis Evseenko
Organizations
- United States Army
- University of Southern California