What are epigenetic cholesterol treatments?
By Lizbeth He
When walking through a grocery store, it is very common to see claims that a food is ‘heart healthy’ and can ‘lower cholesterol.’ Cholesterol is a substance found in blood that is needed to build healthy cells. However, high cholesterol levels can accumulate into fatty deposits, impeding blood flow in the arteries. This can increase the risk of chest pain, heart attacks, as well as stroked (“High cholesterol”). While it is true that eating a diet that it high in fiber, omega-3 fatty acids, and plant sterols can help lower cholesterol levels (“Cholesterol: Top foods to improve your numbers”), researchers have now turned to a new, innovative technology to tackle this issue: epigenome editing.
In the past few decades, genome editing has been in the spotlight, especially with the CRISPR technology. This process involves irrversibly changing an organism’s DNA by inserting, replacing, or deleting a part of the DNA sequence in order to reduce unfavorable traits. On the other hand, editing the epigenome changes the “chemical tags that are bound to DNA and affect gene activity” (Ledford). This is different from gene editing as it is reversible, more subtle in the degree of alterations, and less prone to harmful side effects (Kaiser). Additionally, it can edit while still leaving the main DNA sequence untouched (Sather). Because of these advantages, epigenome editing has been the focus of many new research efforts.
Recently, a study involving mice proved successful as scientists were able to edit their PCSK9 gene, which regulates cholesterol levels. To do this, the scientists designed molecules called ‘zinc-finger proteins’ that bind to specific sequences in the genome, similar to the CRISPR-Cas9 technology. Then, these zinc-finger proteins were infused with pieces of three other proteins. Together, they attached methyl groups that silence the effects of dangerous viral sequences in the genome onto the DNA. Within a month of the treatment, the mice’s cholesterol levels significantly dropped (Ledford). This study’s success left many optimistic about epigenome editing as a potential solution to high cholesterol levels.
Beyond just lowering cholesterol levels, editing the PCSK9 gene was also able to maintain these low levels for long periods. Researchers tracked the mice’s cholesterol levels for another 330 days, and their levels stayed low and showed no sign of increasing back to their original states (Ledford). These results are very hopeful, as it implies that the positive impacts of epigenetically editing the PCSK9 gene could last for upwards of an year. Compared to previous treatments for high cholesterol levels, such as having to take statin drugs everyday, epigenome editing is a more long-lasting and efficient treatment (Howe). Now, scientists are actively searching for ways to apply similar methods onto humans. This involves researching other potential reagents that can efficiently edit human genes, similar to how the zinc-finger proteins worked in the mice. More extensive testing is required to ensure the safety epigenome editing, starting with smaller animals, bigger animals, and then potentially humans (Howe). Eventually, if evaluated as safe, this could be a viable way to address many health conditions.
Epigenome editing is a revolutionary and rapidly evolving field that may potentially be the solution to numerous genetic issues. In addition to controlling cholesterol levels, other studies have shown its potential impact on silencing MYC, a cancer-related gene that has been difficult to target through conventional methods (Ledford). Breakthrough studies in lowering the cholesterol levels of mice is just the first of many beneficial epigenetics applications to come.
Works Cited
"Cholesterol: Top foods to improve your numbers." Mayo Clinic, 7 Mar. 2024,www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/cholesterol/art-20045192#:~:text=Oatmeal%2C%20oat%20bran%20and%20high%2Dfiber%20foods&text=Soluble%20fiber%20is%20also%20found,day%20decreases%20your%20LDL%20cholesterol.
"High cholesterol." Mayo Clinic, 11 Jan. 2023, www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/symptoms-causes/syc-20350800.
Howe, Nick Petrić. "Could This One-time ‘epigenetic’ treatment control cholesterol?" Nature, 28 Feb. 2024, www.nature.com/articles/d41586-024-00609-4#:~:text=11%3A05%20Controlling%20cholesterol%20with%20epigenetics&text=Now%2C%20researchers%20have%20shown%20the,for%20epigenetic%20therapeutics%20for%20humans.
Kaiser, Jocelyn. ""Better than CRISPR? Another way to fix gene problems may be safer and more versatile." Science, 1 June 2022, www.science.org/content/article/better-crispr-another-way-fix-gene-problems-may-be-safer-and-more-versatile.
Ledford, Heidi. "‘Epigenetic’ editing cuts cholesterol in mice." Nature, 28 Feb. 2024, www.nature.com/articles/d41586-024-00563-1.
"PCSK9 Gene." MedlinePlus - National Library of Medicine, medlineplus.gov/genetics/gene/pcsk9/.
Sather, Blythe. "Epigenetic editing: the next generation of genetic medicine." Drug Target Review, 7 July 2023, www.drugtargetreview.com/article/110654/epigenetic-editing-the-next-generation-of-genetic-medicine/.
