In some ways, a lasting traumatic brain injury (TBI) can be the worst kind of injury a person can endure in life. A TBI occurs when the brain is injured by force, and depending on the area affected, an individual is left with difficulty functioning and interacting with their environment. Our movement, sensation, communication, memory and learning is processed and controlled by the brain. When these functions are damaged, the interaction with our world is damaged as well.

Treating traumatic brain injuries may be one of the most emotionally and professionally difficult tasks. In an instant, the development of a person’s years of learning and communication can be erased from an injury such as a blow to the head, possibly leaving someone with the mental capacity and behavior of a toddler. Someone with a traumatic brain injury is often easily confused, unpredictable with their speech and actions, and occasionally aggressive as their frustration with communicating increases and appropriateness is inhibited. I recall treating an older gentleman who was the victim of violence, and just asking him to turn his head caused nausea, visual difficulty, and confusion in following just that simple command.

TBI’s can be divided into three main categories: mild, moderate, and severe. A mild injury often encompasses the kind of TBI that many people experience during their lifetime: a short-lasting concussion with possible loss of consciousness of up to a few minutes. Symptoms are often absent or mild, with some resulting nausea or headache. In a moderate injury, the force of the injury is greater and someone can be unconscious for up to 15 minutes with more lasting symptoms.

The third category is severe TBI’s, which can result from an event such as gunshot wound or the force of an explosion. Severe TBI’s cause permanent damage to the brain and leave lasting effects from which a person generally does not every fully recover. These chronic and lasting effects greatly affect a person’s ability to move, work, communicate with people, and function in society.

Until recently, treatment for people with chronic TBI’s was limited, but there is now hope for progress. A recent study by Chou et al introduced ISRIB, a drug tested in UCSF’s lab which was able to reverse the effects of a TBI in mice. This was done by inhibiting a stress response in the brain commonly associated with TBI. The integrated stress response has been shown to be chronically activated in someone with a TBI, affecting the hippocampus’ ability to store memory and influence healthy cognition. In addition, the drug was able to assist in synthesis of proteins which contribute to learning, in a process called Long Term Potentiation (LTP).

Because the effects of a severe traumatic brain injury can last for months or years before improving, results of treatment for TBI are often slow and inconsistent. Generally, there is no effective protocol treating chronic TBI’s because they are so varied in origin and presentation. This is why the breakthrough from UCSF is so impactive. To possibly reverse the effects of brain damage offers extensive hope and potential for TBI survivors, their families, and their care team.

The absolutely amazing aspect of ISRIB is that it affects chronic effects of TBI. Chronic effects of an injury are very difficult to reverse as the system has often acclimated to its chronic state, making the effects more stable and difficult to change. It is incredible that a drug has been developed to not only inhibit the pathway of a TBI, but reverse its deleterious and long-lasting effects. The potential implications of this medications are massive, possibly allowing people with TBI’s to not only restore memory but continue learning.

Thus far ISRIB has only been tested in mice, and the next phase is move it forward for human testing. ISRIB was licensed in 2015 to Calico, a California-based company which owns rights to discoveries in Dr. Walter’s biochemistry lab at UCSF.

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