Status of precision medicine approaches to traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a serious condition in which trauma to the head causes damage to the brain, leading to a disruption in brain function. This is a significant health issue worldwide, with around 69 million people suffering from TBI each year. Immediately following the trauma, damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI. In the hours-to-days that follow, secondary damage can also occur, leading to chronic outcomes. TBIs can range in severity from mild to severe, and can be complicated by the fact that some individuals sustain multiple TBIs, a risk factor for worse long-term outcomes. Although our knowledge about the pathophysiology of TBI has increased in recent years, unfortunately this has not been translated into effective clinical therapies. The U.S. Food and Drug Administration has yet to approve any drugs for the treatment of TBI; current clinical treatment guidelines merely offer supportive care. Outcomes between individuals greatly vary, which makes the treatment for TBI so challenging. A blow of similar force can have only mild, primary outcomes in one individual and yet cause severe, chronic outcomes in another. One of the reasons that have been proposed for this differential response to TBI is the underlying genetic differences across the population. Due to this, many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment. In this review, we will discuss the research detailing the identification of genetic risk factors for worse outcomes after TBI, and the work investigating personalized treatments for these higher-risk individuals. We highlight the need for further research into the identification of higher-risk individuals and the development of personalized therapies for TBI.

Association of Cadherin-Related Family Member 1 with Traumatic Brain Injury

“…TBI manifests as a swiftly progressive ailment, with some patients exhibiting rapid responses within weeks, and others enduring prolonged complications. Researchers have extensively probed genetic variability using genetic polymorphisms that exacerbate TBI outcomes (Reddi et al 2022 ; Jordan 2007 ). Notably, individuals carrying the ε4 allele following mild TBI exhibited diminished neuropsychological outcomes compared to those lacking this allele (Liberman et al 2002 ).…”

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

“…It is now well established that the mechanisms underlying key drivers of secondary injury, such as inflammation and oxidative stress, are not static but undergo change over time [ 8 , 68 , 126 ]. With this understanding, it may be possible to predict what cellular and molecular mechanisms are most likely contributing to secondary injury at a particular stage of injury, however, it is known that patients show a high degree of variability in their pathophysiologic response following TBI [ 127 ]. Therefore, combined treatments must be based on not only a detailed understanding of “typical” secondary injury evolution but also refined and fine-tuned in accordance with the patient’s individual development of secondary injury to best treat TBI.…”

Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury

“…Outcomes between individuals following TBI greatly vary, making antioxidant treatment or other treatments for TBI so challenging [ 228 ]. The “one-size-fits-all” approach to TBI medicine that has been followed for many years is questionable.…”

“…The “one-size-fits-all” approach to TBI medicine that has been followed for many years is questionable. Due to this, many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment [ 228 ]. TheFDA-approved novel biomarkers for TBI screening, such as GFAP and UCH-L1, which are released from the brain into the bloodstream within 12 h of injury [ 229 ].…”