While some people are prone to heart disease despite healthy lifestyles, some others seem immune to the world’s leading cause of death – even if they smoke, don’t exercise or have high blood pressure or other proven health risks.

“Some people are simply born with genes that seem to make it impossible for them to have heart disease,” said Kiran Musunuru, M.D., Ph.D., a widely recognized cardiovascular genetics researcher at the University of Pennsylvania.

Such rare and seemingly illogical health situations that are based on a person’s genetic makeup fascinate Musunuru, who hopes to unlock some of heart disease’s greatest mysteries through new genetic research discoveries.

Musunuru recently received a Meritorious Achievement award from the American Heart Association for his work using human genetics to identify new ways to prevent heart disease and for introducing innovative approaches to genetics education to the association’s national conferences.

“Despite many talented investigators studying heart disease for many decades, we haven’t done so well in figuring out how to prevent heart disease,” Musunuru said. “Once you get past statins and aspirin, we don’t have many medications that reduce the risk of heart attack. That’s pretty astounding.”

But Musunuru, who earlier this year received the government’s highest honor for early-career science and engineering professionals from President Barack Obama, may be on course for an important discovery through his work developing a “vaccine” that could prevent heart attacks.

Musunuru, the son of a cardiologist, grew up in Florida fascinated by the science of space exploration.

“It meant going to Kennedy Space Center to watch shuttle launches, and building model rockets and launching them from my front yard, and an intense passion for space science,” he said. “More than anything, that’s what got me interested in science.”

Until recently, Musunuru taught students and ran his own research lab at Harvard University, his alma mater, and worked at Brigham and Women’s Hospital.

In the spring he moved to the University of Pennsylvania in Philadelphia, where his focus on a developing cutting-edge therapies to prevent heart disease continues.

“We have unusual individuals on both sides of the spectrum: Those who follow a healthy lifestyle and get heart disease. More intriguingly, there are those who should have a heart attack — they’ve done everything ‘bad’ — but their arteries are clean as a whistle. Their hearts are protected. There’s not a hint of disease.”

What’s protecting them? That’s what researchers like Musunuru want to know.

“If we can take people with good genes and extend the benefit of those genes to the entire population, there’s the potential to sharply curtail the incident of cardiovascular disease,” Musunuru said.

Recent breakthroughs in the cholesterol arena serve as a powerful example of this potential, he said.

In 2003 French researchers found a mutation in a gene called PCSK9 while studying families with extremely high cholesterol and early heart attacks. Their bodies removed much less LDL (or “bad”) cholesterol than people without the mutation. Three years later, researchers in Texas discovered “good” mutations in the same gene, with the opposite effect. It caused people to produce much less of the PCSK9 protein, resulting in very low LDL cholesterol and dramatically slashing heart attack risk.

Their finding paved the way for drug makers to develop two new medications that are now on the market. In a nutshell, they are antibodies that are injected every few weeks to block the PCSK9 protein.

“With these medications, you can potentially give a high-risk patient some of the benefits enjoyed by somebody born with a ‘good’ PCSK9 mutation, when it comes to heart disease risk,” Musunuru said.

The same principle is behind his work to develop a vaccine to prevent heart attacks and strokes.

“The concept is to directly introduce the ‘good’ mutations into average people, permanently, so that with one shot they experience the same reduction of cholesterol levels and coronary disease risk as the people who were fortunate enough to inherit the good mutations,” he said. “The vaccine would target the liver, which is where PCSK9 is produced.”

The vaccine has lowered cholesterol levels in mice up to 40 percent just a few days after they received it. Musunuru said he can foresee the first in-human clinical studies happening within the decade.

“The prospect that we have a viable vaccination strategy that could potentially help millions of people avoid cardiovascular disease is what keeps me going,” he said. “Anything that could have a large impact in reducing cardiovascular disease would be an important milestone in improving the human condition.”

Photo by Tim Sharp