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Prevention of the Post-Traumatic Fibrotic Response in Joints: a Critical Preclinical Evaluation of an Antifibrotic Antibody

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[Technical Report, Annual Report]

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Our research addresses the problem of posttraumatic joint stiffness, a pathology that reduces the range of motion ROM ofinjured joints and contributes to the development of osteoarthritis. The fundamental hypothesis that drives the current study isthat unwanted consequences of the fibrotic response to joint injury may be prevented or limited by targeting the formation ofcollagen fibrils, a main component of the fibrotic mass. Key observations from our studies are i in comparison to the nontreatedcontrol, deposition of newly-formed collagen fibrils in posterior capsules from injured knees of rabbits treated with theantifibrotic antibody is reduced significantly, ii treatment with the antibody-based therapeutic does not cause any side effects,iii the healing of injured joints is not affected by treatment with the therapeutic antibody, iv mechanism of action of theantibody indicates blocking collagen fibrillogenesis by blocking procollagen molecules and increasing their degradation.Conclusion of these experiments will explain the utility and safety of the anti-collagen I antibody applied to reduce to blockexcessive fibrosis associated with joint injury.

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[A, Approved For Public Release]