New therapeutic strategies in the treatment of traumatic brain injury by targeting the LEctin Activation Pathway of complement
The Lectin Pathway (LP) of complement activation has emerged as one of the key players in the mediation of post-traumatic inflammatory pathology of various organs. The LEAP project is based on the hypothesis that LP drives a disease promoting phenotype within the pathophysiology of traumatic brain injury (TBI) and that modulating LP dependent inflammation and tissue loss can markedly improve the clinical outcome. LEAP will apply basic-science and clinical approaches to characterize the events that trigger LP activation in TBI and to assess the therapeutic utility of clinically tested inhibitors or modulators of LP functional activity. Specific objectives of the project will include: i) identification of the key molecules and the pathogenic cascades by which the LP determines to the outcome of TBI injury in a clinically relevant mouse model; ii) assessment of the features of LP activation and their association with clinical parameters in TBI patients; iii) identification of appropriate therapeutic target/s and pharmacological tool/s; iv) definition of appropriate protocols and therapeutic opportunities to facilitate the introduction of a significantly improved clinical treatment of TBI pathology. The unique combination of a clinically relevant mouse model, the availability of highly specific molecules that have already been clinically tested and approved, or that are in development for other indications, highlight the translational promise of LEAP programme.
Imaging techniques, Molecular modelling techniques, Pharmacology, Behavioural methodologies, complement system, lectin pathway
2017 - 2021
Maria Grazia De Simoni (Coordinator)
Anna M Planas
United Kingdom (MRC)