Traumatic Brain Injury

Traumatic Brain Injury

A primary focus of Resolys Bio is the use of oxidized streptolysin O (oSLO) to treat chronic traumatic brain injury (cTBI). Chronic traumatic brain injury (“cTBI”) is a term used to describe concussions that have not completely healed – where patients have not returned to their pre- injury state. It is not a single event but the result of multiple events evolving over time. Some researchers describe the same phenomenon as “Persistent Post-Concussion Syndrome”. Before talking about oSLO and its benefits, we want to clarify some terms commonly used in describing this condition.

How Bad Was the Initial Concussion – Mild, Moderate or Sever

When concussions occur, they have been typically classified as mild, moderate or severe using the criteria in the table below. These categories do not reflect the complexities of this condition.  However, they have been widely used historically and although imprecise and outdated, remain
common in the language describing concussion.

All concussions – mild, moderate and severe – go through three healing phases – fast, slow and virtually no healing. Concussions in the slow or no healing phase are commonly called chronic traumatic brain injury or chronic TBI. There is no clear agreement on when to use this term. Physicians have been known to use it as early as 90 days post-injury, and very few would hesitate to use it one year post-injury. It should be remembered that cTBI is not a different disease; it is just a different stage of concussion that is demonstrating little or no further healing.

cTBI is often misunderstood because the lay public confuses long-term chronic TBI that has not healed with short-term concussions that heal within a year. Each year there are 2.8 million concussions in the US 3 and about 60% (1.7 million) heal within a year 4 , 5 . However, about 1.1
million every year move into the slow healing and no healing stages shown above which define cTBI. While studies show additional recoveries between year 1 and year 2 post-injury, we have
found no published studies which indicate that cTBI patients – mild, moderate or severe – as a group improve much after year two.

All chronic TBI patients, however, are not the same and have different symptoms and degrees of affliction. For example, many patients are not completely independent and need full time care, part time care, or help in leaving the home to shop or to drive in the community. For those who are independent, many are not able to be employed with their pre-injury responsibilities and/or to maintain the family and social relationships that they had before their injury.

As a result, cTBI represents one of the largest unmet medical needs in the U.S. health care market today. Each year there are more new cases of cTBI in the United States than all new cases of breast, prostate, lung and colon cancer combined. Academics estimate the pool of cTBI cases with long term disabilities exceeds five million Americans [6] . However, because this estimate starts with hospital admissions and does not include outpatients, data has been developed that lead us to believe that this number is much larger when physician office and emergency room cases are included. How much larger is debatable, but not likely to be a few percentage points. A CDC analysis of the economic burden of TBI – updated since publication for higher incidence and inflation – indicates that the direct cost/lost productivity of non-fatal TBI likely exceeded $60 billion in 2020 [7 , 8] .


Chronic TBI is not just a problem for veterans and professional athletes. According to the CDC, “Traumatic brain injury (TBI) is a leading cause of death and disability among children and young adults in the United States.” Approximately half of diagnosed TBI incidents are the result
of motor vehicle, bicycle or pedestrian-vehicle accidents, with falls coming in second at 20- 30% [7]. Though representing a smaller percentage, TBI has become known as the signature wound of the wars in Iraq and Afghanistan, with over 250,000 service members sustaining a TBI. As football and other sports injuries have gathered headlines in recent years, they have distracted from the reality that virtually all sports – including cheerleading, wrestling and water polo – give rise to concussions and may be contributing TBI cases that are underreported or not fully recognized by parents.

Large but Largely Invisible Epidemic

Per the CDC:

“The long-term impairments and disabilities associated with TBI are grave and the full human cost is incalculable. Yet because these disabilities are not readily apparent to the public – unlike a broken leg, for example – TBI is referred to as the invisible epidemic. These disabilities, arising from cognitive, emotional, sensory, and motor impairments, often permanently alter a person’s vocational aspirations and have profound effects on social and family relationships.”

The effects of cTBI are typically felt throughout the remaining lifetimes of its victims. A recent
study from Canada reports over thirty-five different symptoms arising from a traumatic brain injury [9] . Some of the obvious categories include:

But its invisible, not-so-obvious consequences can be the most devastating:

And there are varying degrees of affliction arising from both the degree of severity and the location of the principal damage. Chronic TBI does not take a life in the short term as do diseases like heart attacks and cancer. In
essence, cTBI victims lose the life they used to live and become trapped with a “new normal” – perhaps not observably handicapped but not what they used to be. With limited treatment options, the effects of cTBI are typically felt throughout the remaining lifetimes of its victims.

The impact on victims and their families is often devastating. Many survivors of severe TBI fail to completely recover and require ongoing medical treatments and care. It is estimated that over a lifetime, it can cost between $600,000 and $1,800,000 to care for a survivor of severe TBI [10] . One survey of employment after TBI suggests that at least 60% of those who experience TBI with a severity that requires “in facility” rehabilitation is unemployed two years after the event [11] . cTBI also has an impact on longevity and survival, even though it may not be obvious right away. The CDC reports that victims of moderate to severe TBI have a nine-year lower life expectancy than those impacted by other traumas [12] . Chronic TBI increases risks for stroke (100%), epilepsy (300%), depression (200%), psychosis (500%) and risks for death in those with moderate to severe TBI are increased from seizures (5000%), drug poisoning (1100%), infections (900%), pneumonia (600%) [13] .

Despite the high financial and social costs of TBI, not a single drug has been approved to date for treatment of traumatic brain injury, much less long-term chronic TBI [14] .