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In This Issue:
Christine Seidman, MD
Hypertrophic cardiomyopathy is a disease that occurs when the heart muscle thickens, causing the heart to weaken. Recent work from the lab of Christine Seidman, MD, director of the BWH Cardiovascular Genetics Center, has uncovered how the disease may be prevented, and it involves reducing production of a mutant protein.
According to researchers, the findings are a first step toward one day treating or preventing hypertrophic cardiomyopathy, which is the leading cause of sudden death in athletes and sudden heart-related death in people under 30 in the U.S.
"There's really no treatment for hypertrophic cardiomyopathy right now," said Seidman. "You can treat symptoms like chest pain or an arrhythmia [irregular heart beat], but that's not getting at the fundamental problem. While the application of this strategy is in the very early stages, it shows considerable promise."
More than 1,000 different mutations that can cause hypertrophic cardiomyopathy have been identified across approximately 10 genes that make heart muscle proteins. People with the disease have one "good" copy and one "bad" copy of one of these genes.
Studying one of the mutations that causes particularly severe disease, the research team targeted a "bad" gene while leaving the "good" gene alone. Using pre-clinical models, they created and injected a genetic tool designed to home in on the single disease-causing mutation and stop it from making its harmful protein.
By suppressing the "bad" gene, the mechanism was able to reduce production of the mutant protein by about 28 percent-enough to prevent hypertrophic cardiomyopathy characteristics, such as heart muscle overgrowth, cell disorganization and scarring, for about six months.
"For all intents and purposes, the heart looked normal," said Seidman. "Wonderfully normal."
The team also developed a strategy to silence many different mutations by targeting common genetic sequence variants that occur only in the "bad" copy of the gene.
Researchers plan to investigate whether they can continue to stave off disease in pre-clinical models with booster shots, reverse disease damage or reduce hypertrophic cardiomyopathy-related arrhythmias.