A Novel Therapeutic Peptide for Treating Stroke

DESCRIPTION provided by applicant Our goal is to develop a novel peptide therapeutic to alleviate brain and vascular injury after hemorrhagic and ischemic stroke Vascular injury is a leading cause of death in the United States with approximately Americans suffering stroke with deaths each year Those who survive are frequently disabled resulting in over one million US stroke victims living with varying degrees of impairment in the US alone These statistics translate into actual costs to healthcare systems and in lost productivity I costs attributed to stroke were $ billion and that figure is projected to reach $ billion by In vascular injury including hemorrhagic and ischemic stroke one of the key damaging factors results from the breakdown of red blood cells and hemoglobin As an oxygen carrier hemoglobin is essential to our survival However in vascular injury the hemoglobin breakdown leads to the release of toxic levels of hemin This excess hemin sets off a series of events that are deleterious to the injury site and cause the death of neuronal cells A potential solution to this damage is a peptide therapeutic agent that would serve as a high capacity scavenger of the toxic hemin released due to hemoglobin breakdown in bleeding events Recently Ewa Bienkiewiczandapos s research group at Florida State University demonstrated that a N terminal peptide fragment from the prion protein OR can sequester toxic hemin and reduce neuronal cytotoxicity and improve neurofunction in intracerebral hemorrhage mouse model These findings provide the basis for the development of a novel peptide therapeutic to be used following stroke Since OR is derived from a protein involved in stroke defense mechanisms this peptide can be thought of as a boost to the natural response our bodies use to combat damage triggered by vascular injury A second peptide called A OR has been designed to bind hemin more efficiently than OR and provide greater efficacy to reduce neuronal damage than OR following bleeding due to stroke The objective of this proposal is to complete biophysical and functional characterization of OR and A OR and select one to advance into clinical development The proposed SBIR Phase studies have three specific aims determine the hemin binding efficacy of A OR compared to OR using biophysical methods establish a cell based potency assay for measuring the efficacy of OR based peptides and demonstrate that A OR is more effective than OR at reducing brain damage in an intracerebral hemorrhage mouse model PUBLIC HEALTH RELEVANCE On a global scale there are million strokes per year accounting for million deaths These numbers are expected to rise by over the next decade This project aims to develop a novel peptide therapeutic to alleviate brain and vascular injury after hemorrhagic and ischemic stroke Successful commercialization of this peptide therapeutic would ultimately provide a profound front line medical advancement in the treatment of stroke related brain and vascular injury and a significant decrease in both morbidity and mortality caused by stroke