Newton 001 Development of new GPCRs interacting drugs to treat inflammatory diseases

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The overwhelming systemic inflammatory response triggered by acute infection (sepsis) and its progression into septic shock can lead to progressive organ dysfunction. This condition has a 70-90% mortality rate and is a major public health problem both the UK and Brazil. In Brazil there has been a dramatic increase in the number of sepsis-associated deaths (9.8% in 2002 to 16.5% in 2010). A major challenge in the treatment of sepsis-induced cardiovascular collapse is the fact thatit is not responsive to standard vasopressor and inotropic treatments. This situation is aggravated in populations where healthcare provision is not readily accessible, either for socio-economical or geographical reasons, leading to exacerbation of the underlying infection. The proposed work intends to exploit recent knowledge of the ability of drugs to bias responses from cell surface receptors to particular intracellular signalling pathways in order to develop inotropic and vasopressor treatments that are effective in sepsis.