Clinical utility of serum biomarkers for the management of neonatal Hypoxic Ischemic Encephalopathy (HIE) on a point-of-care device

DESCRIPTION provided by applicant Systemic asphyxia occurs in of births and can lead to hypoxic ischemic encephalopathy HIE Between and of neonates with HIE die or have permanent deficits Although hypothermia is the standard of care for HIE we cannot differentiate patients who respond to hypothermia from non responders The primary goal of this project is to conduct a proof of concept study to validate biomarkers that will rapidl and accurately identify individuals likely to respond to hypothermia or who will die We will measure two serum biomarker levels obtained during the first hours of life with the goal to stratify neonates with HIE into three groups responders to hypothermia non responders at high risk for surviving with neurological and or developmental deficits and neonates who die We will also examine relationships between biomarker levels and brain injury assessed by MRI days after birth Based on data using Ubiquitin C terminal hydrolase L UCH L and glial fibrillary acidic protein GFAP as biomarkers of brain injury in several neurological conditions such as TBI and stroke we will examine the potential of these protein biomarkers to distinguish the three groups Our central hypothesis is that GFAP and UCH L are elevated in neonates with HIE and that changes in these proteins will predict response to hypothermia and death We will determine if analysis of these biomarkers can assist in early and accurate diagnosis of HIE predict responders vs non responders to hypothermia predict brain damage magnitude as assessed by MRI or death Specific Aim a Supplement existing serum sample base of patients with additional samples from no less than patients treated with hypothermia We are currently banking samples from control healthy neonates n and clinical controls n from neonates assessed for jaundice Specific Aim b Complete assay analysis of UCH L and GFAP from all serum samples Specific Aim a Determine whether pre treatment concentrations of the biomarkers UCH L and GFAP can predict the response to hypothermia assessed by volumetric MRI days after birth or death We will also determine the temporal changes of biomarkers during the course of hypothermic treatment Specific Aim b Determine if increased levels of UCH L and GFAP or their ratios measured within hours of birth predict death or the volume of brain injury assesses by volumetric MRI days following birth Commercialization potential Banyan Biomarkerandapos s Inc www banyanbio com has completed enrollment for a FDA sanctioned patient international Pivotal Trial ALERT TBI www clinicaltrials gov to determine the clinical utility of UCH L and GFAP to supplement acute diagnosis of mild and moderate TBI in adults A successful completion of this study will extend the applicability of the biomarkers to HIE afflicted neonates PUBLIC HEALTH RELEVANCE This grant seeks to examine the clinical utility of blood based biomarkers analyzed from samples taken within hours of birth to predict whether neonates having hypoxic ischemic encephalopathy HIE will respond to treatment with hypothermia The study will also examine whether changes on biomarker levels will predict and or reflect the magnitude of brain injury or death Based of Banyan Biomarkers Inc extensive experience in developing biomarkers of brain injury this proposal has significant commercial potential