Introduction

Inventors at the Uniformed Services University of the Health Sciences (USU) identified deiminated proteins and their autoantibodies that can be used as potential biomarkers for blast-related traumatic brain injury (TBI). This research addresses a significant health challenge faced by military personnel and athletes who experience repeated mild TBIs, leading to chronic neuropathologies.

Applications and Advantages

• Diagnostic Tool: Development of a multiplex diagnostic platform that assesses autoimmune responses related to blast injuries using frontal cortex brain tissue, blood, CSF, urine, saliva, stool, and synovial fluid.
• Early Detection: Enables early diagnosis of underlying pathologies associated with repeated mild TBIs such as impaired learning and memory and emotional and mood imbalances.
• Therapeutic Monitoring: Assists in evaluating patient responses to therapeutic interventions. The red lines in the figure below illustrate where therapeutics can be applied to inhibit protein deimination.

Innovation Description

The invention identifies specific brain proteins that undergo aberrant deimination in frontal cortex, and then be identified in the blood, CSF, urine, saliva, stool, and synovial fluid tissue in rodents, and swine, due to single or repeated mild blast injuriesand human brain samples from people who had experienced serious car crashes. Deimination alters protein structure and function, creating unique proteomic signatures indicative of injury. The presence of autoantibodies against these modified proteins suggests an autoimmune response contributing to chronic conditions such as impaired cognition and mood disorders. The proposed diagnostic platform aims to identify these proteins and their sequences, facilitating both diagnosis and monitoring of treatment efficacy.

Figure 1:A sequence of events that can result in a brain-specific
autoimmune response to injury and the parts in the sequence
where therapeutic interventions can be enacted to prevent injury.

Inventors:

• Gregory P. Mueller, Ph.D. (USU)

Intellectual Property Status:

Patent applications are pending in the United States (17/051,857), and Europe (19723592.2)