Cholesterol reduced thanks to a new gene editing treatment, in America in a limited-scale experiment they managed to reduce dangerous cholesterol. The study involved only 10 patients, but suggests that cholesterol can be permanently reduced with a single treatment for patients at risk of heart disease.
Reports Gina Kolata, health editor for the New York Times for years. The patients in the study had severe heart disease that caused chest pain and heart attacks. They volunteered for an experimental cholesterol-lowering treatment using gene editing, unlike anything tried before on patients.
The result, announced by Boston-based Verve Therapeutics at a meeting of the American Heart Association, showed that the treatment appeared to significantly reduce cholesterol levels in patients and appeared to be safe.
The study involved just 10 patients, with an average age of 54 years. Each had a genetic abnormality, familial hypercholesterolemia, which affects about a million people in the United States. But the findings could also point the way to millions of other patients around the world battling heart disease, which remains a leading cause of death. In the United States alone, more than 800,000 people have heart attacks each year.
In Italy, in 2020, there were 227 thousand deaths from circulatory diseases.
And while further studies will be needed in a broader range of patients, gene editing experts and cardiologists have said the treatment has the potential to transform preventative cardiology.
Impressed by the data and the potential it shows, pharmaceutical giant Eli Lilly paid $60 million to partner with Verve Therapeutics and agreed to acquire additional rights to Verve’s programs for an additional $250 million. If editing continues to look promising, Eli Lilly plans to help with larger studies.
“Until now, we’ve thought of gene editing as a treatment for very rare diseases for which there were no other treatments,” said Dr. Daniel Skovronsky, Eli Lilly’s chief scientific officer and medical officer. “But if we can make gene editing safe and widely available, why not tackle a more common disease?”
The new study was led by Dr. Sekar Kathiresan, CEO of Verve. Patients received a single infusion of microscopic lipid nanoparticles containing a molecular factory inside them to modify a single gene in the liver, the site of cholesterol synthesis. The PCSK9 gene increases levels of LDL cholesterol, the bad one. The plan was to block it.
The small lipid spheres were transported through the blood directly to the liver. They entered the liver cells and opened up, revealing two molecules. One instructs the DNA to create a gene editing tool and the other is a guide to bring the editing tool to the gene that needs editing.
The treatment “is almost science fiction,” said a cardiologist not involved in the study.
The gene editing tool, explains Gina Kolata, works like a pencil and an eraser. The eraser erases one letter of the target gene and the pencil writes a new one, deactivating PCSK9.
The goal: a single cholesterol-lowering treatment that results in lifelong protection from heart disease.
Patients received varying doses. LDL levels in the three who received the highest doses dropped by 39 to 55 percent.
In the small study, those who received the highest doses experienced flu-like symptoms for a few hours. Two patients had serious adverse events that the study’s independent data safety and monitoring committee deemed to be the result of serious underlying heart disease. The board advised the researchers not to stop the study.
One had a fatal cardiac arrest five weeks after receiving the infusion. An autopsy showed that several of his coronary arteries were blocked.
The other patient had a heart attack the day after the infusion. It turned out that he had had chest pain before receiving the infusion but he had not reported it. If investigators had known, he would not have received treatment.
The treatment is the culmination of studies that began a decade ago, when researchers discovered rare but healthy individuals with cholesterol levels that seemed incredibly low. The reason was that their PCSK9 gene had mutated and no longer worked. As a result, these people were protected from heart disease.
This led to the development of antibodies to block the gene. Patients inject themselves with the antibodies once a week. Then came a twice-yearly injection of RNA that prevents the production of PCSK9.
Even if gene editing works, its application to young people at risk for heart disease is a long way off. But, Dr. Gulati said, early gene editing of younger patients with genetically high cholesterol levels could prevent hardening of the arteries.
“It could be incredible medicine,” he said.
This all depends on the success and safety of gene editing and how long its effects last. The first patient was treated just six months ago. But an earlier study in monkeys lasted two and a half years, and the gene editing results had a lasting effect.
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