Prevention of the Post-Traumatic Fibrotic Response in Joints: a Critical Preclinical Evaluation of an Antifibrotic Antibody
Abstract
Objectives: The main objective of this project is to help wounded Soldiers recover from injuries to their extremities by applying a therapeutic antibody to reduce post-traumatic joint stiffness. Since clinical interventions available today to limit post-traumatic joint stiffness are sparse and their outcomes are disappointing, our research is needed and timely. Rationale: Soldiers are uniquely prone to suffer from joint injuries due to the risks associated with their military activities. One of the major complications of trauma to the joints is post-traumatic joint stiffness that severely limits range of motion, causes pain, and makes it impossible to resume military duties. Post-traumatic joint stiffness mainly results from the formation of scar tissue that alters the normal function of injured joints. Although post-traumatic joint stiffness may be partially reduced by surgery and lengthy physical therapies, the effectiveness of these interventions is not fully satisfactory. To prevent joint stiffness, we developed a therapeutic antibody that blocks the formation of the unwanted fibrotic scars that are responsible for stiffening of damaged joints. During the initial stage of our research, we demonstrated the efficacy of this antibody to reduce joint stiffness in a relevant animal model. Here, we will move our antibody-based inhibitor closer to clinical trials by defining the safety and efficacy parameters for this therapeutic agent. Ultimate Applicability of the Proposed Study: 1. Target Patients: The main group of patients we target includes Soldiers that have sustained trauma to their joints. We aim to apply our antibody-based therapeutic soon after joint injury to prevent excessive buildup of unwanted scar tissue. We have scientific evidence indicating that this treatment reduces post-traumatic joint stiffness, thereby lessening pain and facilitating speedy recovery. 2. Potential Clinical Applications: The research we propose represents the next logical step in moving our approach to limit post-traumatic joint stiffness from the bench to the clinic. Although our main target here is post-traumatic joint stiffness, the potential clinical applications of our technology for diseases that involve the formation of unwanted fibrotic scar tissue are numerous. These applications may include reducing burn scars, limiting abdominal adhesions, blocking lung fibrosis, and others. As clinically applied antibody-based treatments are generally safe, we expect no significant risks associated with our proposed approach. Timeline for Patient-Related Outcomes: Our study fits into the category of development of a biologic therapeutic agent. For any therapeutic agents, the following steps must be taken before an agent may be applied in preclinical and then clinical tests: (1) identifying a clinical problem; (2) defining a relevant therapeutic target; (3) developing a therapeutic agent; (4) testing the selected agent in simple experimental models of a disease; (5) testing the selected agent in relevant animal models that resemble human disease; (6) developing relevant biomarkers; (7) checking the concentration-dependent efficacy and potential side effects; and (8) moving toward clinical studies with human patients. Thus far, we have successfully completed the first five stages of the development of our proposed approach to limit joint stiffness. The study we propose now addresses the next two interim stages (i.e., steps 6 and 7) on the path to clinical studies. We are confident that we will complete these stages within the 3-year duration of the proposed study. We also expect that the success of this proposal will help attract commercial partners and move this approach into clinical trials within a few years. Benefit for Service Members: Post-traumatic joint stiffness is a serious problem for military personnel suffering from injuries to the extremities. In addition, the long-term consequence of post-
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810554
Entities
People
- Andrzej Fertala
Organizations
- Thomas Jefferson University
- United States Army