From Bench to Bedside: The Role of Science in Treating a Deadly Disease

Leslie was fascinated by human genetics by the time she went to college and has been passionate for decades about unraveling genetic contributions to disease. A long path that took a few twists and turns ultimately led her to a longstanding goal: to develop treatments for genetic diseases where none existed. It started with mapping genes to human chromosomes. The next phase led her to be an academic scientist. At the University of Colorado, Leslie’s lab studied how certain muscle mutations lead to disease. In other words, how a small DNA change leads to an often fatal crisis in the heart. It is this kind of work, sometimes called basic research, that lays the foundation for the bridge from bench to bedside. The disease that her lab continues to study is called familial hypertrophic cardiomyopathy, a long way of saying a big sick heart that runs in a family. This disease is most notable for killing young athletes, sometime with no prior symptoms. Geneticists identified what genes, if mutated, cause this disease. What Leslie will do today is to share how a great deal of searching led to the first FDA approved drug in 2021 by MyoKardia, the company she co-founded in 2012. MyoKardia has since been acquired by Bristol Myers Squibb. Prior to this drug, the only effective treatment for this disease was a heart transplant. In fact, familial hypertrophic cardiomyopathy is the leading cause of sudden death in young people. Once tools became available, it was possible to determine which members of a family carried that mutant gene, frequently after someone in the family suffered a cardiac arrest. Having the knowledge of your genotype is an important advance. But, what do you do with that information when there is no treatment? Many were told to stop athletic activity; others were followed by a cardiologist, but this was a very anxious way of life. Leslie’s talk will tell the story of finding a treatment for a fatal genetic disease of the heart.