Novel Proteomic Biomarkers of Brain injury in New-Borns

Dr. Divyen Shah, Royal London Hospital/Barts and the London School of Medicine, QMUL

A Study of Novel Proteomic Biomarkers of Brain Injury in Term Newborns with Hypoxia-Ischemia

After brain injury, whether traumatic or due to condtions such as stroke, further deprivation of blood or oxygen to the brain tissue may worsen brain injury in all age groups. The neonatal brain is particularly vulnerable and deprivation of blood or oxygen to a baby through the placenta often occurs unexpectedly prior to or at the time of delivery which can have catastrophic consequences, often leading to disability or even death. Until recently, only supportive treatment could be provided. However, since 2010, cooling treatment is routinely used in full term newborn babies at risk of brain injury which, when commenced within the first six hours followiNovel Proteomic Biomarkers_Divyenng birth has been shown to reduce death and disability in survivors (NICE guidance 2010). At present there are no objective tests at the bedside that inform our selection of babies for cooling. With the clinical criteria currently used, we are certain that some babies who may benefit from treatment get missed and other babies who may not benefit are treated unnecessarily, thus subjecting them to risk and unnecessary use of resources. Hence, there is a desperate need for readily accessible biological markers that can be used at the bedside to assist in selecting babies for brain saving treatments as well as allowing us to monitor their progress with the treatment. With this study we aim to develop a blood test that can be administered at the bedside that will allow better selection of babies for brain saving treatments, such as cooling, and also allow us to determine the long term outcomes for individual babies who have suffered from lack of blood or oxygen. Various biological markers can be used but we are proposing to study the proteome, which refers to the total protein production by a single organism. The proteome changes in response to stresses and injury which result in unique signatures that may allow determination of timing as well as severity of pathology of specific organ systems. Specific changes in several blood proteins have been identified in adults with strokes and other brain pathologies. However, they have yet to be studied in newborn babies using state-of the art technology as proposed in this study. With Research and Ethics approval (REC 13/LO/17380) and informed consent from parents, we have collected blood samples from 45 such newborn babies, with varying degrees of brain injury. With our industry partners Proteome Sciences plc we aim to identify specific proteins and their levels in blood samples using an analysis technique termed mass spectrometry, which we will relate to severity of brain abnormality using short term outcomes of neurologic examination and brain imaging and electrical activity. Through this study we will define protein changes that specifically identify severity of brain abnormality and damage in babies who have suffered from oxygen and blood deprivation to the brain. Furthermore, the data may allow the development of new neuroprotective therapeutics through identification of pathways or targets that could be modified by small molecules or agents to limit injury. The success of this study will assist paediatricians to refine selection for brain saving treatments as well as allowing prediction of outcomes. Furthermore, the findings from this study will lead to a larger multicentre phase two study and the potential development of a baby brain injury assay.