How does a common genetic cause of Brugada syndrome take effect?

A structural and/or signalling role for ventricular NaV1.5 in a murine model for Brugada syndrome

BHF-funded researchers in Cambridge are investigating the molecular biology underlying Brugada syndrome. Brugada syndrome is a dangerous inherited heart condition that can cause sudden death. About 30 per cent of cases are caused by abnormalities in a protein called Nav1.5, which initiates the heartbeat. These researchers intend to find out more about how changes in Nav1.5 lead to Brugada syndrome, and reveal clues to ways we could treat it effectively. The team have genetically engineered mice to have a reduced amount of Nav1.5 proteins. These mice show symptoms similar to Brugada syndrome, including thickening and scarring in the heart known as fibrosis, which is the result of high levels of a hormone called TGF-beta1. The researchers want to uncover why a lack of Nav1.5 leads to this dangerous build-up of TGF-beta1. With this funding, they will identify molecules that Nav1.5 normally interacts with. They will then screen DNA from people with Brugada syndrome to see if they have any changes in these interacting molecules. If so, this could open new avenues for therapies to combat the dangerous effects of Brugada syndrome.