Revolutionary research has revealed that controlling high cholesterol, one of the main risk factors for cardiovascular disease, can be achieved for up to a year with a single dose of treatment. The discovery involves a gene editing technique capable of deactivating a gene associated with LDL cholesterol, known as bad cholesterol, keeping its levels controlled in patients for a prolonged period.
The innovative research was presented at the Congress of the European Society of Cardiology and had its results published in the prestigious New England Journal of Medicine. To assess its effectiveness, the therapy was administered to 15 participants, who were monitored for approximately one year after application.
The relevance of the study is highlighted by the impact of high cholesterol, recognized as one of the major drivers of cardiovascular problems. Data from the Ministry of Health indicate that, in Brazil, heart attacks and strokes are responsible for more than 300,000 deaths annually, with approximately 40% of the population suffering from high cholesterol.
Currently, the standard treatment for high cholesterol includes the continued use of statins, which, although effective, require lifelong adherence. This new approach represents a significant advance, proposing a single-dose solution for the management of a chronic disease.
Despite the promising results, the research is still at an early stage, focused mainly on evaluating the safety of the therapy. However, the next phase has already begun with a larger group of individuals, and new results are expected by the end of 2026, a period in which negotiations with regulatory agencies for a phase 3 study should also begin.
This research establishes a new paradigm for gene therapy, a method that directly modifies DNA to combat diseases. Historically applied to rarer conditions, this technology now has the potential to treat common diseases, expanding its reach and impact.
For geneticist Lygia da Veiga Pereira, gene therapy is breaking barriers. She explained that this approach opens up ways to treat diseases prevalent in the population, which intensifies the impact of genetic treatments and highlights the importance of deepening knowledge in these areas.
Understand how genetic editing works to combat cholesterol
The human body generates two types of cholesterol, and LDL acts as the main conductor of fat through the bloodstream.
However, excessive transport of LDL can lead to the deposit of fat in the arteries, forming plaques that obstruct blood flow and increase the risk of heart attack and stroke.
The new therapy employs CRISPR technology, described as “molecular scissors.” This tool locates a particular sequence in DNA, performs an exact cut and, therefore, deactivates a specific gene.
In this context, the targeted gene is ANGPTL3, found in liver cells, the organ responsible for most of the production of cholesterol and triglycerides in the body.
Normally, ANGPTL3 produces an enzyme that makes it difficult to eliminate LDL and triglycerides from the bloodstream. By deactivating this gene with CRISPR technology, scientists were able to prevent the formation of the enzyme, optimizing the body’s metabolism of these fats.
The inspiration for the treatment came from the observation of a population in Italy, where individuals were born with a mutation that disables ANGPTL3. These people had consistently low levels of cholesterol and triglycerides throughout their lives and minimal occurrence of heart disease, a pattern that gene therapy seeks to replicate.
What the preliminary survey results indicate
It is important to highlight that the data is initial, but promising. In patients who received the maximum dose, a reduction of almost 80% in the ANGPTL3 enzyme in the blood was observed, leading to a decrease of approximately 50% in LDL and triglyceride levels, maintained for at least one year without new applications.
The persistence of index control is considered one of the most impactful points of the study by researchers. This fact suggests that gene editing has achieved an adequate volume of liver cells to generate lasting clinical benefit.
Additionally, the modified cells demonstrated the ability to replicate continuously, transmitting the genetic change in ANGPTL3 to new cells. This explains the maintenance of positive results even after one year of administering the treatment.
Future perspectives and challenges of the new treatment
Cardiologist Elzo Mattar, who serves as director of the Arterial Hypertension Department of the Brazilian Society of Cardiology (SBC) and is a professor at the São José do Rio Preto State School of Medicine (Famerp), sees great potential in single-dose therapy for chronic conditions, such as dyslipidemia and hypertension. For him, the great advantage would be to combat the high dropout rate and lack of adherence to long-term treatments.
Mattar stated that this represents a “dream therapy” for patients who need continuous treatments, but frequently interrupt them. He points out that this interruption can lead to serious complications, which could be prevented by simplifying the treatment regimen.
The specialist also indicated that the new approach could be a valuable alternative for people who do not react satisfactorily to oral medications, such as patients with familial hypercholesterolemia, who have a dysfunction in the LDL receptor.
However, the cardiologist tempers optimism by mentioning that the regulatory approval process will be lengthy, and that the initial cost of treatment will likely be a limiting factor. Mattar clarified that, “even if its efficacy and safety are proven and approved, this is an expensive treatment that should not be immediately accessible to the population.”
Ricardo Kazunori, cardiovascular surgeon at BP – the Portuguese charity in São Paulo, also evaluated the research. He said that, although it represents a significant advance for chronic patients, the therapy is still far from being a practical reality.
Kazunori shared his experience, saying that he treats “critically ill patients who require surgery due to the consequences of high cholesterol” and need “even stricter” control of their levels. He concluded that, although such therapy could revolutionize treatment for these people by offering more precise control, it is crucial to wait for the next stages of scientific research, as the study is only initial.
