Novel Target and Lead Compound to Reverse TBI-Induced Alzheimer s-Related Dementia
Abstract
It is estimated that >1.4 million Americans each year suffer a traumatic brain injury (TBI), defined as a blunt or penetrating injury to the head that alters brain function. Importantly, TBI is also a major health issue in the U.S. military, with estimates of TBI prevalence as high as 23% of returning service members (including both moderate/severe and mild concussive TBI). Mild (concussive) and moderate/severe TBI have both been linked to immediate and delayed development of long-term disabilities; predominantly reduced working memory, difficulty learning new information, execute function, and reasoning. Interestingly, a similar array of cognitive deficits are observed in patients with Alzheimer’s disease (AD) and AD-related dementias (ADRD). Relevant to the current Program Announcement, there is an emerging consensus that TBI is associated with increased risk of future AD and ADRD, and military personnel are increasingly living with TBI and associated risk of cognitive decline. Thus, it is critical to improve our understanding of the etiology of TBI-induced dementia and cognitive dysfunction with the goal of identifying new therapeutic targets to improve quality of life for the thousands to millions of military and civilian individuals living with TBI. We have developed a new lead compound that inhibits a signal that is activated specifically during the brain’s response to injury, thus minimizing the likelihood of side-effects. Our data using our new compound shows that giving this new compound immediately after TBI prevents the development of post-injury dementia. Remarkably, we have also observed the ability of this compound to reverse post-injury dementia symptoms when given at delayed time-points after the development of dementia. Therefore, the aims of the current study focus on a new therapeutic target, which has the potential to delay and even possible reverse injury-induced dementia symptoms, thus greatly improving the quality of life of soldiers, veterans, and civilians living with the burden of brain injury.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810727
Entities
People
- Paco S Herson
Organizations
- United States Army
- University of Colorado Denver