Heart disease

A Small Study Demonstrates the Efficacy of a Novel Gene Editing Treatment in Reducing Harmful Cholesterol Levels

The study encompassed a mere 10 individuals, yet it indicates that cholesterol levels can be effectively lowered in patients who are susceptible to heart disease through a solitary treatment.

A small group of patients were suffering from severe heart disease that resulted in chest pain and heart attacks. Despite trying various cholesterol-lowering medications, they were unable to achieve the recommended levels suggested by cardiologists. As a result, they decided to participate in an experimental treatment that involved gene editing, which had not been attempted on patients before. Verve Therapeutics of Boston reported on Sunday that the treatment had significantly reduced cholesterol levels in the patients and was deemed safe. The trial involved only 10 patients, all of whom had familial hypercholesterolemia, a genetic abnormality that affects approximately one million people in the United States. However, the findings could have implications for millions of other heart disease patients worldwide, as heart disease remains a leading cause of death. In the United States alone, over 800,000 people suffer from heart attacks annually.

1. Gene editing experts and cardiologists have expressed their belief that the treatment has the potential to revolutionize preventive cardiology, although further trials involving a wider range of patients are still required. Fyodor D. Urnov, a gene editor at the Innovative Genomics Institute in Berkeley, Calif., described this development as a significant milestone, stating that it signifies a major advancement in the field. Recognizing the promising data and potential, pharmaceutical giant Eli Lilly has invested $60 million to collaborate with Verve Therapeutics and has also secured additional rights to Verve's programs for $250 million. Eli Lilly intends to support larger studies if the editing technique continues to demonstrate promising results.

Dr. Daniel Skovronsky, Eli Lilly's chief scientific and medical officer, expressed a shift in perspective regarding gene editing. Previously, it was believed that gene editing should be reserved for rare diseases without any alternative treatments. However, Dr. Skovronsky now questions this notion and suggests that if gene editing can be made safe and accessible to a wider population, it could be utilized for more common diseases as well.

In a recent study led by Dr. Sekar Kathiresan, chief executive of Verve, patients were administered a single infusion of microscopic lipid nanoparticles. These nanoparticles contained a molecular factory capable of editing a specific gene in the liver, which is responsible for cholesterol synthesis. The targeted gene, PCSK9, is known to elevate levels of LDL cholesterol, commonly referred to as the "bad" cholesterol. The objective of the study was to inhibit the function of this gene.

1. The liver was directly targeted by the tiny lipid spheres, which penetrated liver cells and released two molecules. One molecule instructs DNA to create a gene editing tool, while the other molecule guides the editing tool to the gene that requires editing. This innovative treatment has been described as resembling science fiction by Dr. Martha Gulati, the director of preventive cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles and the president of the American Society for Preventive Cardiology, who was not involved in the trial. The gene editing tool functions as both a pencil and an eraser, with the eraser removing one letter of the target gene and the pencil writing in a new one, effectively turning off PCSK9. The ultimate objective is to develop a single cholesterol-lowering treatment that provides lifelong protection against heart disease. Patients were administered varying doses, with the three individuals who received the highest doses experiencing a 39 to 55 percent reduction in LDL levels, which was sufficient to bring them closer to their cholesterol target.

In a small study, participants who received higher doses of the treatment experienced flu-like symptoms for a few hours. However, two patients with underlying severe heart disease had serious adverse events. One patient had a fatal cardiac arrest five weeks after receiving the infusion, and an autopsy revealed blocked coronary arteries. The other patient had a heart attack the day after the infusion, but had not reported chest pain before receiving the treatment. The study's independent data safety and monitoring board advised the researchers not to stop the study. The treatment is the result of a decade-long study that began with the discovery of individuals with mutated PCSK9 genes, which protected them from heart disease. The development of antibodies to block the gene led to patients injecting themselves with the antibodies once a week, followed by a twice-yearly RNA injection to prevent PCSK9 from being made.

It appeared plausible that these treatments, along with statins for individuals with easily manageable cholesterol levels, could potentially offer a solution to the problem of heart disease.

However, heart disease continues to persist as a deadly condition. Even after individuals have been diagnosed with heart disease, less than 60 percent of all patients adhere to taking a statin. Merely a quarter of them opt for the more potent and effective high-intensity statins, as stated by Dr. Gulati.

"Initially, patients may take the medication, but then they either forget or believe they no longer require it," she explained. "This occurrence is more common than one might anticipate."

Dr. Michelle O'Donoghue, a cardiologist at Brigham and Women's Hospital, highlighted the fact that due to patients frequently neglecting their prescribed pills or injections, there is a growing interest in gene editing for a one-time treatment that would provide a lifelong response.

Dr. Kathiresan at Verve Therapeutics drew inspiration from his family history. His uncle and grandmother succumbed to heart attacks, while his father experienced one at the age of 54. Then, on September 12, 2012, his 42-year-old brother, Senthil, returned from a run feeling dizzy and sweaty. He was having a heart attack and unfortunately passed away nine days later.

Prompt: Rewrite differently this text: At that moment, Dr. Kathiresan said, he vowed to find a way to prevent what had happened to his brother from happening to anyone else.

1. Dr. Kathiresan made a promise to himself to discover a solution that would prevent others from experiencing the same fate as his brother.

2. After witnessing what happened to his brother, Dr. Kathiresan was determined to find a way to ensure that no one else would have to go through the same ordeal.

3. Dr. Kathiresan was resolute in his determination to uncover a remedy that would prevent others from suffering the same fate as his brother.