Traumatic Brain Injury

A primary focus of Resolys Bio is the use of oxidized streptolysin O (OSLO) to treat chronic traumatic brain injury (cTBI). TBI can occur from a single event such as an automobile accident or from multiple concussions such as those experienced by athletes and those serving in the military. Chronic traumatic brain injury is often defined as a brain injury that has persisted for more than one year and has failed short-term remedies.

Traumatic brain injuries are caused by mechanical insult or rapid acceleration/deceleration of the neuronal cells of the brain, and they have two attributes that make treatment and developing new treatments more challenging:

  • cTBIs are not a single pathophysiologic event, but a series of such events that unfold over time. While the initial mechanical insult can lead to immediate disruption of brain tissue, including contusions, hemorrhage, and axonal shearing, the downstream damage to brain tissue can continue for days, weeks, and even months.1
  • cTBIs involve multiple factors at work, not a single cause. The ongoing disease process can include subsequent cellular and metabolic events such as disruptions to cellular calcium homeostasis, increased generation of free radicals and lipid peroxidation, mitochondrial dysfunction, and inflammation, among others.2

Furthermore, differences in the nature and severity of an injury make it difficult to arrive at a standardized evaluation that can guide treatment. With all these challenges, we find it easy to understand why it has been so difficult for most of the 100+ acute TBI clinical trials completed to date to show significant clinical benefits.3 To the extent that OSLO can deliver these benefits, it represents a first-in-class product candidate with potential worldwide revenues of $10 billion.


  1. Xiong Y, Mahmood A, Chopp M. “Animal models of traumatic brain injury.” Nature Reviews Neuroscience,  Feb;14(2): 128-142, 2013.
  2. Xiong y, Mahmood A, Chopp M. “Emerging treatments for traumatic brain injury.”  Expert Opinion on Emerging Drugs. March; 14(1): 67-84. Doi:10.1517/14728210902769601, 2009.
  3. Stein DG. “Embracing failure: What the Phase III progesterone studies can teach about TBI clinical trials.” Brain Injury. 2015;29(11):1259-72. Epub 2015 Aug 14. Review.