Grant: Operating Grant

Background: Long QT syndrome (LQTS) is a cardiac electrical disorder caused by malfunction of ion channels, which can lead to life-threatening dysrhythmias (irregular heartbeats) and unexpected sudden death. LQTS can be inherited due to naturally occurring subtle alterations (mutations) in ion-channel proteins in the heart. These alterations make one unique type of ion-channel proteins unstable in the cell membrane, leading to a reduced amount of proteins and causing the disease. Presently, there is no means available to correct prolonged QT intervals in patients. Objective: The aim of our project is to establish that healthy fatty acids can stabilize certain mutant proteins on the cell surface. This would enhance the amount of the proteins on the cell surface, thereby providing a new treatment for the affected patients. Description of the research project: We will create alterations of the protein (mutations) to mimic the disease-causing protein in humans. We will grow the altered proteins in cultured cells. The data we obtained so far indicate that these protein alterations make the protein unstable in the cell surface and non-functional. We will test whether healthy fatty acids can restore the protein stability in the cell surface and rescue the protein function. Significance: In the last decade, drug-induced LQTS has been the single most frequent reason for a drug to be removed from the market. Inherited LQTS is responsible for most unexpected sudden death in young otherwise healthy individuals. This project aims to explore a novel and effective means using healthy fatty acids to treat the life-threatening heart disease, LQTS, and reduce its impact on our society.