Prevention of the Post-Traumatic Fibrotic Response in Joints: A Critical Preclinical Evaluation of an Antifibrotic Antibody
Abstract
We successfully tested in vivo the validity of the concept that blocking the formation of fibrotic scars limits post-traumatic joint stiffness. Specifically, we rationally engineered a therapeutic anti-collagen I antibody (referred to as ACA) that targets collagen I molecules and prevents their participation in scar formation. In the course of our previously-funded research, we validated our approach in a relevant animal model of post-traumatic joint stiffness. Here, we plan to move our research from the proof-of-concept phase closer toward clinical tests. We have reached important milestones that define the course of our proposed study. These milestones include: (i) verifying fibrotic scarring as a valid target to limit post-traumatic joint stiffness; (ii) engineering a clinically-relevant form of the ACA to inhibit fibrotic scarring; and (iii) validating in vivo the efficacy of the ACA to limit post-traumatic joint stiffness. Here, we will continue our preclinical research to achieve the following goals: (i) to define the concentration-dependent safety and efficacy of our ACA; (ii) to determine the effects of the ACA on the healing of joint tissues; and (iii) to define clinically-relevant biomarkers to monitor the effects of the ACA-based treatment of injured joints. Achieving these goals will provide a launching platform for future clinical tests. Objective/Hypothesis. The main objective of this study is to limit post-traumatic joint stiffness in military personnel by employing an antibody-based blocker of fibrotic scarring. We hypothesize that applying this therapeutic antibody will reduce post-traumatic joint stiffness without causing any significant unwanted side effects.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1164044
Entities
People
- Andrzej Fertala
Organizations
- Thomas Jefferson University