Validation of the Treatment Outcomes of a Fixed-Dose Combination Therapeutic in a High-Fidelity Porcine Model of Traumatic Brain Injury
Abstract
In 2019, 166 Americans died every day from a traumatic brain injury (TBI). A TBI is a sudden injury that causes damage to the brain. These injuries include falls, assaults, sports/recreation accidents, motor vehicle accidents, and firearm-related injuries. The estimated annual direct and indirect costs of TBI are $76.5 billion. When a person experiences a TBI, the neuronal and nonneuronal cells in the brain react to the injury with a series of biochemical and physiological processes. Some of these processes worsen the damage caused by the initial injury and damage the blood-brain barrier, which protects the brain by only allowing certain substances to pass through. One type of nonneuronal brain cell is microglia, which participate in immune responses in the central nervous system. Microglia produce substances to prevent injury-related inflammation, clean up damaged tissue, and promote restorative processes. However, the microglia themselves can become dysregulated and do the opposite: produce substances that promote inflammation, which worsens the brain damage worse and impedes brain healing and recovery. Thus, inflammation in the brain plays a big role in the processes underlying TBI. Many studies have treated patients with TBI with medications that target inflammation, but these medications have not improved their outcomes. This is thought to be related to the complex processes that occur after the initial injury and the lack of a good model of human TBI that can be used to evaluate potential medications. Inflammatory Response Research, Inc. (IRR), which is a drug development company, has found that patients with inflammatory disorders and conditions have good results when treated with combination therapy involving levocetirizine (Xyzal) and montelukast (Singulair). Levocetirizine is an antihistamine used to treat allergy-related congestion, while montelukast is used to treat asthma. Dr. B. Chandler May, the President and CEO of IRR, has successfully used the combination of levocetirizine and montelukast in his clinical practice to treat patients with various inflammatory disorders, including polytrauma, sepsis, and autoimmune neutropenia. Dr. May has also used the levocetirizine/montelukast combination to treat a limited number of patients with TBI and found that these patients exhibited clinical improvements. These medications are thought to be effective in patients with TBI because of their effects on the immune system, helping prevent the deleterious processes that occur in the brain downstream of the initial injury. Herein, IRR is proposing the development and testing of a levocetirizine and montelukast injectable. The injectable will be assessed in a swine model of TBI. Compared to rodents, which have most commonly been used in studies of TBI, swine are thought to better model the human brain because of the shape and makeup of the brain are more similar between swine and humans than between rodents and humans. Hopefully, the results of this study will lead to testing of the combination therapy in human clinical trials in patients with TBI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211012
Entities
People
- Bruce May
Organizations
- United States Army