Novel Therapeutic Small-Molecule Strategy Targeting Bone Morphogenetic Protein Signaling to Prevent Upper Extremity Heterotopic Ossification
Technical Report,30 Sep 2017,29 Sep 2018
Regents of the University of Michigan Ann Arbor United States
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Purpose To validate prophylactic strategies to prevent trauma induced heterotopic ossification using validated small animal models. Scope Heterotopic ossification is one of the most challenging problems associated with reconstruction following high-energy trauma wounds due to its insidious development which often leads to chronic pain, open wounds, and loss of range of motion. Ultimately, HO significantly limits soldier function, readiness, and redeployment. Patients who develop these signs or symptoms may undergo radiographic imaging to identify HO, at which point it has already matured and the only option remaining is surgical excision. This results in further morbidity to the patient, and costs for the military healthcare system for the operation, and post-operative management. Furthermore, patients may often develop recurrence which necessitates additional operations, and even successful excision is unable to address the sequelae of HO including chronic pain, open wounds, and loss of function. Our goal is to transform the management strategy for patients with trauma-induced HO, by first targeting two synergistic signaling pathways involved in the development of HO, and then by precisely timing in high-risk patients to minimize duration and maximize efficacy, in order to prevent HO formation. Major Findings TAK1 signaling plays a central role in traumatic heterotopic ossification. NG25 is effective in preventing traumatic HO. NG25 decreases osteogenic differentiation of HO progenitor cells.
- Medicine and Medical Research
- Anatomy and Physiology