Heart Health

An Anti-Cholesterol Injection

An injection against heart attacks? It just might be possible, scientists say.

Scientists at the Harvard Stem Cell Institute (HSCI), in collaboration with researchers at the University of Pennsylvania, have developed an injection that reduces cholesterol levels in mice by 30 to 40 percent. In humans, that translates to a 90 percent reduction in heart attack risk.

“For the first iteration of an experiment, this was pretty remarkable,” said Kiran Musunuru of HSCI, an assistant professor in Harvard’s Department of Stem Cell and Regenerative Biology (SCRBl. Musunuru added, though, that it could take a decade to get the new approach into a clinical trial in humans.

The study focused on altering the function of a liver gene, PCSK9.

Earlier research found that PCSK9 was a cholesterol regulator. But the findings have been paradoxical: in 2003, scientists in France discovered that the mutations gene seemed to be responsible for high cholesterol level and heart attacks. That mutation is extremely rare.

However, a research group in Texas found that 3 percent of the population have mutations of PCSK9 that have the opposite effect. People with that “good” defect have heart attack risks that range from about 47 to 88 percent below average.

“Our reasoning was that nature has already done the experiment; you have people who have won the genetic lottery,” said Musunuru. “They are protected from heart attack, and there are no known adverse consequences. So that led us to reason that if we could find a way to replicate this, we could significantly protect people from heart attack.”

The replication involved turning normal PCSK9 genes into those with the “good” effect.

“What we were thinking was that, with this genome-editing technology, we can do something we couldn’t do before: make permanent changes in the genome at the level of the DNA,” Musunuru said. We can actually go to the source. So the question was whether we can use genome editing to make normal people like people born with the ‘good’ mutations.” The answer, in mice, was yes.