Introduction to Lipoprotein(a)
A single dose of an experimental drug dramatically reduced levels of a deadly form of cholesterol, often thought to be untreatable, for up to one year.
Lipoprotein(a) is a type of cholesterol that lurks in the body, undetected by routine tests and undeterred by existing drugs, diet or exercise.
The findings, cardiologists say, are a critical step toward treating the millions of Americans genetically predisposed to abnormally high levels of lipoprotein(a), or Lp(a).
The Impact of Lipoprotein(a)
“It’s remarkable,” said Dr. Eric Brandt, director of preventive cardiology at the University of Michigan Health Frankel Cardiovascular Center in Ann Arbor, who wasn’t involved with the new research. “These drugs have the potential to nearly eliminate that lipoprotein.”
People with high levels of Lp(a) — some 64 million adults in the U.S. — are at extremely high risk of cholesterol buildup in their arteries. That buildup raises their odds of heart attack, stroke and early death from cardiovascular problems.
Research and Findings
Findings from an earlier trial of the Eli Lilly drug, called lepodisiran, showed the drug was safe.
The latest study, a Phase 2 clinical trial funded by Lilly, included 320 people. One injection, researchers found, cut Lp(a) levels by 93.9% after six months. After a year, the effects waned, but only slightly, with levels measured at 88.5% lower than the baseline. People in the trial who got a second dose at six months had a 94.8% reduction at the one-year mark.
“This is a major source of cardiovascular morbidity and mortality,” said Dr. Steven Nissen, chief academic officer of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic and lead researcher of the lepodisiran trial. “We have never been able to treat lipoprotein(a) until now,” he said.
How Lepodisiran Works
Lepodisiran works by targeting the mRNA, or messenger RNA, that tells the body to make Lp(a). Messenger RNA carries instructions to proteins in the body to produce certain substances, in this case, Lp(a). The drug works by essentially shooting the messenger.
A Triple Threat
Understanding Lipoprotein(a)
Lipoprotein(a) is dangerous in three ways: It sticks to LDL (the “bad” cholesterol), making it more likely to clog arteries; it’s particularly good at causing inflammation; and it tends to lead to blood clots.
Routine blood cholesterol tests could look for Lp(a) but do not — largely because there’s never been an effective treatment for it.
Real-Life Impact
A diagnosis of high Lp(a) was a shock to Donald Kosec, 61, of Stow, Ohio. Kosec said he never had any of the typical risk factors for heart disease: He exercised regularly, kept a healthy weight, and checkups with the doctor showed normal cholesterol and blood pressure levels.
Eight years ago, when he was 53, Kosec went to his doctor after feeling a little short of breath. It was only then that he learned all of the major arteries pumping blood to and from his heart were blocked. Elevated Lp(a) was the culprit.
Within three weeks, he was having quintuple bypass surgery.
“Going from not having the care in the world to all of a sudden facing your own death, your own mortality,” Kosec said. “It caught me off guard, big time.”
Conclusion
The discovery of lepodisiran and its effects on lipoprotein(a) levels offers new hope for the millions of people at risk of cardiovascular diseases due to high levels of Lp(a). As research continues and these drugs move towards approval, individuals like Donald Kosec may finally have an effective treatment option to manage their condition and reduce their risk of heart attack, stroke, and early death.
FAQs
- Q: What is lipoprotein(a), and why is it dangerous?
A: Lipoprotein(a) is a type of cholesterol that increases the risk of heart attack, stroke, and early death from cardiovascular problems. It is dangerous because it sticks to LDL cholesterol, causes inflammation, and leads to blood clots. - Q: How does lepodisiran work?
A: Lepodisiran works by targeting the mRNA that tells the body to make lipoprotein(a), effectively reducing its levels in the body. - Q: What were the findings of the Phase 2 clinical trial of lepodisiran?
A: The trial found that one injection of lepodisiran cut lipoprotein(a) levels by 93.9% after six months, with levels remaining 88.5% lower than the baseline after a year. - Q: Who is at risk of having high levels of lipoprotein(a)?
A: Approximately 64 million adults in the U.S. have high levels of lipoprotein(a), often due to genetic predisposition. - Q: When might lepodisiran or similar drugs become available for treatment?
A: As research continues and these drugs move through the approval process, they are expected to become available for treating high lipoprotein(a) levels in the future, offering new hope for those at risk of cardiovascular diseases.
