Grant: CIHR Clinician Scientist - Phase 2

In heart muscle cells, the protein troponin complex is the molecular switch that turns contraction on and off with each heartbeat. Troponin is important to the health of Canadians in the following ways: 1) Genetic diseases are caused by DNA mutations that change the structure of a particular protein. The heritable cardiomyopathies are common genetic disorders (about 1:500) affecting heart muscle proteins like troponin, increasing the risk of heart failure and sudden cardiac death. We are studying how the function of troponin is regulated in the healthy heart, and how it becomes dysregulated by mutations. This will allow us to develop drugs to correct the problem. 2) We are designing troponin-specific drugs to correct the effect of mutations that cause the heritable cardiomyopathies. This would improve heart muscle function and restore normal muscle growth, preventing the development of heart failure. We anticipate that these drugs could also be used to treat heart failure caused by other conditions. 3) When the heart is damaged, troponin leaks into the bloodstream, where it can be detected by blood tests used by physicians to diagnose heart damage. In a heart attack, not only is troponin released, but it is also partially digested by enzymes. Right now, conventional blood tests do not distinguish between intact troponin and digested troponin. We are developing a blood test to make this distinction, which will provide more useful information about the cause of heart damage in order to guide treatment. Understanding troponin will help doctors to better diagnose and treat heart disease, which affect over a million Canadians every year.