Researchers have discovered a critical component in the progression of heart failure – a microRNA that blocks a gene responsible for regulating calcium flow within heart muscles. This decrease in gene activity is known to cause heart enlargement and, in turn, impair heart function.
The calcium-regulating gene at the center of the research is SERCA2a, which appears to be blocked by the presence of a microRNA called miR-25. According to researchers, miR-25 pathologically suppresses the production of SERCA2a, which is critical for heart contraction. Declining levels are associated with heart failure.
“Boosting SERCA via gene therapy is a clinically validated approach to treat heart failure and is now in clinical trials,” said co-senior author Dr. Mark Mercola, professor in the Development, Aging, and Regeneration Program at Sanford-Burnham Medical Research Institute and professor of bioengineering at UC San Diego Jacobs School of Engineering.
Researchers were able to identify miR-25 through a functional screening system developed at Sanford-Burnham. The system, which uses high-throughput robotics, allowed investigators to sort through the entire genome for microRNAs related to heart muscle dysfunction. From there, collaborative researchers from the Cardiovascular Research Center at Mount Sinai’s Icahn School of Medicine discovered that inhibiting miR-25’s effects stopped the progression of heart failure in mouse models.
Improved cardiac function and survival were reported, as well.
“The RNA drug should be tested in large animal models, which have greater similarity to human disease,” said Mercola.
According to Mercola, the drug still has to undergo the typical routines of drug development. This includes testing its effects on other tissues, exploring dosage, figuring out how to formulate it and deciding on the route of delivery, among other things. Even so, the discovery marks a breakthrough in heart failure research. Current medications used to treat the condition have yet to address the underlying mechanisms that weaken heart contraction.
Heart failure occurs when the heart is unable to pump enough blood and oxygen throughout the body. According to the U.S. Centers for Disease Control and Prevention, roughly half of all people who develop it die within five years of diagnosis. About six million people in the United States suffer from heart failure.
By Marianne Hayes