• Evaluating anticoagulant Protein C pathway activity in patients with Sickle Cell Disease

    2020 marked the start of 5 new paediatric research projects funded by the National Children’s Research Centre and Children’s Health Foundation, Crumlin. Dr. Roger Preston (RCSI, Principal Investigator), Prof. Corrina McMahon (CHI at Crumlin, co-PI), and Dr. Michelle Lavin (RCSI, co-PI) received funding for their project “Novel therapeutic approach to counter vaso-occlusive crisis in sickle cell disease using engineered activated protein C”.

    What research problem does this project aim to address?

    Sickle cell disease (SCD) is a significant cause of global paediatric illness and death. SCD causes red blood cells to bind to other blood cells and block blood vessels, which can cause painful sickle cell ‘crises’ and stroke to occur. There are only a limited number of therapies currently available to treat SCD. The objective of this study is to evaluate the role of activated protein C (APC), a blood protein with anticoagulant and anti-inflammatory activity, in controlling SCD, with a view to utilising engineered activated protein C variants as potential therapies for the treatment of SCD-associated blood vessel damage.

    What is the proposed approach to solving this problem?

    This study will utilise the newly-established biobank of paediatric SCD blood samples collected as part of the Sickle Vascular Ireland Consortium (SiVIC) study to investigate the role of defective protein C pathway activity in SCD-associated vascular inflammation and occlusion. Specifically, we propose to determine whether the protein C pathway is impaired in individuals with SCD at different disease stages and treatment and investigate whether activated protein C has the potential to mitigate the key molecular events that contribute to SCD blood vessel dysfunction, such as inflammation, blood cell binding to sticky blood vessels and uncontrolled blood coagulation

    How will this research impact on child health?

    Sickle cell disease (SCD) is a significant cause of global paediatric illness and death. Children with SCD are subject to painful crises, anaemia and stroke. Unfortunately, there is a limited understanding of the molecular events that lead to blood vessel occlusions that contribute to crises and therefore a limited number of effective SCD therapies. This study aims to test new therapeutic approaches to reduce the painful symptoms of SCD and meet the urgent, unmet need for novel therapies to enhance care of children with SCD.