Brain Injury and Disease Prevention, Treatment and Research
Abstract
Brain Injury and Disease Prevention, Treatment and Research is focused upon identifying drugs that will interfere with pathological tau prion formation in the brains of service members who are at risk for developing CTE and other neurodegenerative diseases following repeated TBI. Service members who have served in combat and have received repeated impact and/or blast TBIs are at risk for developing chronic traumatic encephalopathy (CTE) and other neurodegenerative diseases which are associated with significant persistent behavioral/neurologic manifestations. Currently, there are no validated means for diagnosing these problems in living patients or drugs to effectively treat them. The overall mission of this program is to develop drug candidates that will effectively block the formation of brain tau prions that can be entered into clinical trials for the prevention and/or treatment of CTE and other neurodegenerative disorders in at-risk active duty and retired service members. Using human brain specimens, CTE has been now shown to qualify as a transmissible tau prion disorder. To date, 319,513 novel chemical compounds have been tested for their ability to interfere with in vitro tau prion formation. Several active compounds have been identified and using medicinal chemistry, we have attempted to improve their bioavailability and lower toxicity profiles. Such candidate drugs are now being tested for efficacy in animal models of tau prion disorders. Part of the progress in this regard is the development of a transgenic rat that overexpresses human tau with the P301S mutation. In addition, new highly sensitive techniques to identify the presence of tau prions in brain samples have been developed.
Document Details
- Document Type
- Accomplishment
- Publication Date
- Oct 01, 2022
- Source ID
- 27e065fca4a60c656a1180e487d663ea