Tailoring treatments for dangerous abnormal heart rhythms

Predicting anti-arrhythmic drug efficacy from the divergent molecular basis of RyR2 dysfunction in genetic arrhythmia syndromes (renewal)

BHF Professor Alan Williams studies abnormal heart rhythms, or arrhythmias, which can be fatal. Although we understand some of the processes involved in arrhythmias, the efficacy of current treatments are variable, and the causes of abnormal heart rhythms sometimes remains a mystery. The team is focusing on proteins called ryanodine receptors, or RyR2. These proteins are channels that enable cells within the heart to handle and release calcium. The movement of calcium within heart cells enables the heart to beat properly. Faults in RyR2 could be important in causing arrhythmias. We need to understand this process so we can prevent dangerous rhythm disturbances developing. Professor Williams is using his own new cell-based tools to investigate how changes to the RyR2 protein lead to abnormalities that underpin severe, early onset arrhythmias. They will use these tools to work out how drugs we currently use to treat arrhythmias, and new experimental drugs, affect these channels. This work will help us understand how protein alterations affect calcium channels, and could reveal new ways to treat people with life-threatening arrhythmias.