Validation of FcgRlla as a potential drug target in sepsis

WT Scheme: Seed Award in Science.

Sepsis is characterised by a severe coagulopathy which is responsible for the high mortality in this disease. This coagulopathy is due to extensive platelet activation and consumption which leads to bleeding due to the subsequent thrombocytopenia and thrombosis due to the platelet activation.
We have shown in vitro that this platelet activation is due to direct interaction between bacteria and platelets. In all of the bacteria tested so far (both Gram-negative and Gram-positive) the platelet receptor for IgG (FcgRIIa) plays a critical role in the activation of the platelets. This makes FcgRIIa a potential drug target in sepsis. Previous work has been compromised by the fact that this receptor is only expressed in higher primates. The availability of transgenic mice that express FcgRIIa make it possible to explore the role of this receptor in sepsis using a mouse model.
The proposal is to establish a sepsis model in transgenic mice and to validate the potential of FcgRIIa as a drug target by testing the ability of antibodies to FcgRIIa to improve outcomes in mouse sepsis models.

Award Date
01 August 2015
Award Value
Principal Investigator
Dr Dermot Cox
Host Institution
Royal College of Surgeons in Ireland
SFI-HRB-Wellcome Research Partnership