There is no medication to stop progressive brain damage after a TBI

Traumatic Brain Injuries (TBI) are one of the leading causes of death and disability in young adults. Every 12 seconds, someone in the United States suffers a new head injury. Head injuries constitute a global epidemic with more than 69 million cases each year worldwide. Yet, to this date, there are no approved pharmaceutical therapies for TBI.

TBI is caused by a blunt impact or a jolt to the head, and most commonly occurs in sports, motor vehicle accidents and military personnel due to training and exposure to blasts. Mechanical forces applied on the head during the impact leads to a primary injury – a physical force that damages brain cells. However, biochemical and physiological processes initiated cause a secondary injury that evolves over a period of hours to days, even months, after the primary insult.

Secondary injuries are multiple, parallel, interacting and interdependent cascades of biological reactions. The major pathways include: excitotoxicity due to the excessive release of excitatory amino acids, Ca2+ influx, mitochondrial dysfunction, release of reactive oxygen species (ROS) and free radicals, exposure to metal ions, neuroinflammation as a result of infiltration of inflammatory cells and release of pro-inflammatory cytokines. The various harmful compounds and activated cell signaling pathways damage the surrounding healthy tissue long after the actual primary injury has occurred.

The acute physical damage that occurs during the primary injury is considered irreversible, so the current TBI treatments aim to stabilize the site during the secondary injury. These include removal of hematomas, interventions to decrease cerebral edema and maintain a normal intracranial pressure and cerebral blood flow, prevention and treatment of complications such as seizures and infections. Many therapeutic agents have been tested to reduce and prevent damage caused by the secondary injury, however, so far none of them have been found to improve the neurological outcome in large phase III clinical trials.

A potential explanation for the failure of previously researched therapies is that many of them target a single aspect of the secondary injury cascade. Medicortex aims to take an alternative approach to TBI treatment by addressing several pathophysiological mechanisms simultaneously using compounds which possess multiple biochemical properties. We hypothesize that minimizing the damage from the primary TBI and stopping the expansion of secondary brain injuries requires a compound which has several neuroprotective functions, such as free metal ion binding (chelating agents), anti-inflammation, anti-oxidation and free radical scavenger action. Medicortex has designed and synthetized these compounds and they were found to be safe in preclinical animal studies. Efficacy of the drugs to halt the secondary injury and improve outcome will be studied in the near future in animal studies.?