Prevention of Heterotopic Ossification by Blocking Innate Immune Response
Abstract
Heterotopic ossification (HO) is the growth of bone in abnormal places like soft tissue or joints. Variable amounts of bone can be formed from small amounts to substantial ones. HO can cause pain and discomfort, limit range of motion, and make the use of prostheses difficult or impossible. There is no current uniformly successful treatment for HO short of surgical excision. Even then bone can reform after surgery. The focus of this grant application is to develop a treatment for HO. The grant application is unusual because it draws on preliminary data of the applicant that HO is very dependent on one form of the immune system that is called innate immunity. Immune defenses come in two forms: innate and adaptive. Innate immunity recognizes molecular patterns commonly used by bacteria, viruses, and other organisms that attack the body to recognize and destroy them. Adaptive immunity makes antibodies against these organisms, which takes more time but which eventually is stronger because not only does it destroy the organism, but it also has memory so that if the same organism is encountered again, the response is very fast and even stronger. It may seem strange that the immune system would be involved in bone formation, but if one considers that in bone repair there is usually injury to the bone, it makes more sense. Apparently the mechanisms our body uses to deal with infection and injury overlap to a large extent since the two often occur together. There are key receptors in innate immunity called "toll-like receptors." The applicant will first prove in a rigorous fashion that certain of these receptors are important in HO. Then inhibitors that block these receptors will be tested for their ability to block HO. Such a treatment for HO would be used in combination with a diagnostic test that detects early HO because the HO must be stopped early, before bone is formed. HO is a major concern for the military because of the continued increasing use of improvised explosive devices. In the wars in Afghanistan and Iraq, HO occurred in a staggering 65% of all combat injuries. However, improvised explosive devices are a concern for civilians as well and their prevalence is increasing.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610649
Entities
People
- Alan R Davis
Organizations
- Baylor College of Medicine
- United States Army