SBIR-STTR Award

We hypothesize that the use of SanFlow (aka polynitroxylated pegylated hemoglobin; PNPH) will ultimately translate to the reduction of mortality and morbidity, including post-traumatic stress disorder, from battle field traumatic brain injury (TBI). Towards that end, the present SBIR Phase 1 proposal will provide safety and efficacy results of SanFlow in a new guinea pig model of traumatic brain injury (TBI) with and without hemorrhagic shock (HS). Previous studies, all successful, were in mice. FDA in Pre-IND response has recognized SanFlow is a neuroprotective resuscitation agent for TBI and HS based on existing mouse data. The present study in a more advanced animal model with greater relevance to humans will set the stage for future Phase 2 studies in minipigs to be submitted at a later date. In mice, SanFlow is safe and efficacious at low unit volume as compared to fresh whole blood: peer reviewed publications have demonstrated SanFlow is efficacious at less than 1/10th the dose of shed fresh whole blood. The proposed safety and efficacy studies in guinea pigs will support IND and Phase I clinical trial protocol design for use of SanFlow as a neuroprotective agent for TBI with or without HS.

An ideal therapeutic for traumatic brain injury (TBI) accompanied by hemorrhagic shock (HS) should serve both as a resuscitation fluid to restore perfusion pressure while directly protecting the brain from secondary injury. Previous work in mice demonstrated that SanFlow is more effective than crystalloid or whole blood in restoring arterial pressure after TBI+HS and reduces neurodegeneration in the hippocampus. In Phase I, we found that resuscitation with SanFlow was superior to electrolytes in restoring arterial pressure and preserving hippocampal viable neurons in a guinea pig model of TBI+HS. In Phase II, we will evaluate the efficacy of SanFlow in a pig model, a large animal with a gyrencephalic brain. The first objective is to manufacture 30 L of SanFlow. The second objective is to evaluate three doses of SanFlow during resuscitation from TBI+HS on 4-day outcome of neuroinflammation, blood-brain barrier permeability, subacute neurodegeneration, and axonal injury. Using the optimal dose of SanFlow, the third objective is ascertain stable protection of neurons and axons over 15 days of recovery. These studies will inform whether SanFlow is capable of mitigating secondary brain injury over a 4-day period, and whether this treatment provides long-term neuroprotection rather than simply delaying neurodegeneration.