POLYNITROXYL HEMOGLOBIN:NEUROPROTECTIVE OXYGEN CARRIER

DESCRIPTION: (Investigator's abstract) Polynitroxyl hemoglobin (PNH) will be developed as a neuroprotective oxygen carrier. PNH is different from 1st generation hemoglobin-based oxygen carriers (HBOCs) in that it has added anti-inflammatory activity in addition to oxygen carrier function. PNH is created by covalently attached nitroxides, an analogue of nitric oxide (NO) in a piperdine "cage," to HBOC. We have shown that PNH is an oxygen carrier with anti-inflammatory superoxide dismutase and catalase mimetic activities. In the Phase I of the present application, we propose to develop PNH as an anti-inflammatory oxygen carrier and demonstrate that it is resistant to oxidative damage in vitro and neuroprotective in vivo. In Phase II of this SBIR application, we propose to elucidate the mechanisms and efficacy of PNH with a hemodilution protocol in clinically relevant brain injury models. In a companion Phase I/Il SBIR entitled "Polynitroxyl Hemoglobin (PNH) : Preclinical Safety," we propose to conduct toxicology studies of PNH for an IND submission to FDA. PROPOSED COMMERCIAL APPLICATION: An oxygen carrying resuscitative fluid with anit-inflammatory activities such as PNH is highly desirable. HBOC products in advanced clinical development, provide only oxygen delivery. Unfortunately, during severe hemorrhage, or trauma, there is significant inflammatory (ischemia and reperfusion) injury. The inflammatory injury often lead to multiple organ failure (MOF). Therefore the use of PNH is to provide better protection against MOF in trauma resuscitation and can be used as a neuroprotective oxygen carrier in ischemic, hemorrhagic and traumatic head injury. The market potential for a 2nd generation HBOC is established to be 3 billion/year.