New therapeutic strategies in the treatment of traumatic brain injury by targeting the LEctin Activation Pathway of complement

点击翻译按钮获取中文摘要

Traumatic Brain Injury (TBI) is an injury to the brain caused by a trauma to the head (head injury). The main causes of TBI are road traffic accidents, assaults, falls and accidents at home or at work. An the UK, approximately 1 million cases with head injury are seen in Accident and Emergency Clinics per year of which 15% require hospitalisation. The damage caused by TBI can be temporary or permanent leading to various degrees of physical, cognitive, and behavioural/emotional impairments or death. The outcome of TBI is determined by the severity of the initial injury and by the degree of the inflammatory response following the injury. Limiting the inflammatory response following the injury is a desirable neuroprotective treatment that can significantly improve the clinical outcome of TBI. This project is based the observationthat a defined pro-inflammatory pathway of the innate immune defence, called the lectin activation pathway of complement, plays a key role in driving inflammation following injury and the investigators have identified the key enzyme that drives this inflammatory response following injury. This enzyme is exclusively made by liver cells and reaches other organs through the blood supply where it is present at very low plasma levels. An effective and long-lasting therapeutic depletion of this enzyme can be achieved by administration of a monoclonal antibody which significantly reduces inflammatory tissue loss as previously shown in experimental models of stroke, myocardial infarction and renal transplantation. The preliminary results in experimental TBI model clearly imply that MASP-2 inhibition will effectively limit post-traumatic inflammation and loss of CNS tissue. This project is likely to deliver the proof-of-principal data required to advance a new and highly neuroprotective clinical therapy to reduce morbidity and mortality following TBI.