Working out the cause of abnormal heart rhythms in Rett syndrome

Investigation of cardiac late sodium current as a therapeutic target in Rett Syndrome

Professor Jules Hancox and his colleagues at the University of Bristol are studying the causes of abnormal heart rhythms in Rett Syndrome, a condition caused by faults in a gene called MECP2. In Rett Syndrome, children initially thrive, but then develop severe problems with language, learning, coordination and other brain functions. In some people with Rett Syndrome, abnormal electrical activity of the lower heart chambers - the ventricles - can lead to dangerous heart rhythm disturbances. The healthy heart’s electrical activity depends on the coordinated opening and closing of proteins called 'ion channels' in heart muscle cells. Results from mice with a faulty MECP2 gene suggest that abnormal heart activity in Rett syndrome may be due to a faulty ion channel that allows sodium to pass into heart cells. These faulty channels may allow too much sodium to enter cells in the ventricles with each heartbeat. In this project, Professor Hancox will collect electrical recordings from whole hearts and single heart cells from mice with Rett syndrome. This will allow him to work out why and how altered sodium channel activity happens in Rett syndrome and if drugs could correct it. He will also find out whether the abnormal rhythms seen in Rett syndrome can be remedied using drugs. This research will help provide insights into the underlying cause of the heart abnormalities associated with Rett syndrome and could identify potential treatments for people with the condition.