Preliminary results from a study show that gene-editing technology can be used to successfully treat a genetic disorder that increases the risk of heart disease. The study, involving 10 patients born with a genetic condition that causes very high cholesterol, found that editing the gene inside the liver can significantly reduce levels of "bad cholesterol." While more research is needed to confirm the approach's safety and effectiveness, these results are being hailed as a potential landmark proof-of-concept that could eventually provide a powerful new way to prevent heart attacks and strokes.

Dr. Deepak Bhatt, director of the Mount Sinai Fuster Heart Hospital, described the data as "really very exciting" and emphasized the need for further research to resolve important questions. The study, conducted by Verve Therapeutics, Inc., in Boston, was presented at an American Heart Association meeting in Philadelphia. Dr. Sekar Kathiresan, Verve's executive officer, described the findings as the first-ever evidence that one can actually rewrite a single DNA letter in the human liver and have a clinical effect. However, some independent scientists remain cautious and highlight the uncertainties, including the long-term safety of this approach.

Heart disease is the nation's leading killer, causing approximately 695,000 deaths each year in the United States. High levels of a form of cholesterol known as low-density lipoprotein (LDL) cholesterol narrow arteries, blocking blood flow to the heart and brain and setting the stage for heart attacks and strokes. Patients born with familial hypercholesterolemia, a genetic disorder that affects an estimated 1 in 250 people, have extremely high LDL levels. While drugs like statins can help reduce LDL levels, many patients fail to take them regularly as prescribed, leaving them vulnerable.

The gene-editing treatment using CRISPR technology offers a potential one-time therapy for those with the genetic condition, as well as for anyone at risk. Researchers used a newer version of CRISPR known as "base-editing," which enables scientists to make very precise changes in DNA. In this case, the editing occurred in liver cells inside the body. Other approaches to gene-editing have required removing cells from the body, editing them in the lab, and then infusing them back into patients.

In the ongoing trial, scientists are infusing different doses of the CRISPR base-editing molecule that reaches the liver to edit the gene called PCSK9, which is necessary for the production of LDL cholesterol. Of the 10 patients treated so far, three received a high enough dose to cause a beneficial reduction in LDL. Two patients experienced reductions of 39% and 48% in their LDL levels, while the patient who received the highest dose saw a reduction of 55% that has lasted at least six months thus far.

While the potential of gene-editing to treat high cholesterol is promising, there are still uncertainties and concerns. Long-term safety and the possibility of unintended genetic changes known as "off-target" effects are areas requiring further investigation. The development of gene-editing techniques has generated excitement, as it could lead to new treatments for various genetic diseases, including cancer, heart disease, AIDS, Alzheimer's, and more. The Food and Drug Administration is expected to approve the first gene-editing treatment for sickle cell disease next month, highlighting the potential for this approach.

Overall, the use of CRISPR for high cholesterol represents a significant development in the field of gene-editing. It offers hope for new, more effective treatments for genetic disorders and has the potential to revolutionize the way heart disease is prevented and managed.

• Q: What are the preliminary results from the study?

  A: The preliminary results show that gene-editing technology can be used to successfully treat a genetic disorder that increases the risk of heart disease.

• Q: How does the gene-editing treatment work?

  A: The treatment involves using a newer version of CRISPR known as "base-editing" to make precise changes in the DNA inside liver cells. This editing targets the gene PCSK9, which is necessary for the production of LDL cholesterol.

• Q: What are the potential benefits of this treatment?

  A: The treatment could provide a one-time therapy for patients with the genetic condition causing high cholesterol and could also be helpful for individuals at risk of heart disease.

• Q: What were the reductions in LDL levels observed in the study?

  A: Of the 10 patients treated so far, two experienced reductions of 39% and 48%, while the patient who received the highest dose saw a reduction of 55% that has lasted at least six months.

• Q: What are the concerns surrounding gene-editing for high cholesterol?

  A: There are concerns about the long-term safety of the approach and the possibility of unintended genetic changes known as "off-target" effects.

• Q: How does high cholesterol contribute to heart attacks and strokes?

  A: High levels of LDL cholesterol narrow arteries, blocking blood flow to the heart and brain, and increase the risk of heart attacks and strokes.

• Q: What other genetic diseases could be treated with gene-editing?

  A: Gene-editing techniques have the potential to be used in the treatment of cancer, heart disease, AIDS, Alzheimer's, and other genetic diseases.

• Q: Are there already effective drugs for high cholesterol?

  A: Yes, drugs like statins are widely used to reduce LDL levels. However, many patients fail to take them regularly as prescribed.

• Q: How does gene-editing using CRISPR differ from other approaches?

  A: CRISPR enables scientists to make precise changes in DNA inside the body, whereas other approaches require cells to be removed, edited in the lab, and then infused back into patients.

• Q: What is the potential impact of gene-editing for high cholesterol?

  A: If further research confirms its safety and effectiveness, gene-editing could provide a powerful new way to prevent heart attacks and strokes.