Prevention and Treatment of Neuroma and Induction of New Nerve Growth
Abstract
Heterotopic ossification (HO) is the formation of bone where it is neither needed nor wanted. Neuroma is a tumor of the nerve itself that occurs in severe nerve injury and is an unsuccessful attempt at the nerve to repair itself. Both conditions can be painful and debilitating, and surgery is currently the only uniformly successful treatment. Although both occur in the civilian sector, they are far more likely to occur in the military where the sometimes severe nature of the injuries is favorable to these conditions. They are particularly prevalent in amputees, causing the additional problem of interfering with the wearing of prosthetic devices. Our laboratory has been working for some time on these problems. In this work, largely supported by the Department of Defense, we have found, unexpectedly, that the two problems are related in that they share several of the same biological steps. Although conventional wisdom has dictated that problems in the formation of bone should arise from cells in the marrow of the bone, in actuality, heterotopic bone formation arises from cells in the nerves. Since neuroma is a tumor that occurs at the end of a nerve that is damaged, this is also a problem of nerves. In the current application, we propose that the two problems can be prevented or treated using a single drug. We show data for a drug that works in rodent models of HO and neuroma and hope to extend this testing to larger animals. This would prepare us for eventual clinical testing of these drugs in patients. The timeline for these drugs to reach the clinic could be as short as 5 years. Although HO is usually viewed as a condition that needs to be eliminated, some of the steps of the process may be the same as those in bone repair. We think that one such step is the repair of nerves, as, regardless of the final position of the bone, without innervation and vascularization it cannot function and ultimately resorbs. We therefore propose to utilize some of the steps that the bone uses to recruit the nerve -- in other words, those steps leading to nerve growth -- but block the steps that lead to bone growth, and place substances or cells that elicit these nerve growth steps in a device or conduit that will allow us to be able to use this system for severed nerves to be successfully repaired. Another important part of the research is gaining an understanding of the fundamental nature of these disease processes to better enable treatment and prevention. Nerves are a very important part of the body in that they are the principal form of communication with the brain. Therefore, nerves have several “barrier” systems that stop most substances from entering. We have also found that it is the breakdown of these barriers during the severe injuries sustained in combat that are the fundamental cause of HO and neuroma. However, such knowledge has also shed light on why certain injuries to nerves cannot heal and provides opportunities to explore methods and agents that might help to enable the eventual healing of even complex and severe nerve injuries.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710628
Entities
People
- Alan R Davis
Organizations
- Baylor College of Medicine
- United States Army