New Gene Editing Treatment Cuts Dangerous Cholesterol in a small study

A small group of patients  with severe heart diseases after trying all the available cholesterol-lowering medications statin volunteered in experimental study that use gene editing to lower cholesterol. The results published from the Verve Therapeutics of Boston at the AHA(American Heart Association) proved that the treatment reduce cholesterol levels and it appears to be safe without side effects. The study was conducted by Dr. Sekar Kathiresan. The trial involved 10 patients on the average age of 54. The patients received a single infusion of microscopic lipid nano particles that contains molecules to edit and block the gene PCSK9 which is responsible of cholesterol synthesis in particular the LDL cholesterol. The lipid spheres were injected through the blood stream to reach the liver. Once into the liver cells the spheres would open up and release two molecules. One of the molecules had instruction for the DNA to create a gene editing tool, the other one is a messenger to bring the editing gene tool to the appropriate gene. The gene editing tool works like a pencil and an eraser. The eraser delete the base of the targeted gene while the pencil writes a new one that will  turn off PCSK9. Patients that received the treatments dropped the level of LDL by 39 55%.

The end goal of this study and of this treatment was and it is to find a way to administer a single cholesterol-lowering treatment that can change the outcome of hearth diseases. Heart diseases are the most common diagnosed diseases and are the leading cause of death in America, by causing nearly 800,000 deaths every year. Most of those are related to cholesterol and LDL type. The connection between LDL and the gene was discovered at first by  French researchers, that found a mutation of the gene PCSK9 , was leading to high level of LDL cholesterols. The mutated gene founded in the French study was then looked at more accurately and it was discovered that there were people with a different mutation of the same gene that could have lower LDL cholesterol and protect from the disease. In fact, people with either one or both PCSK9 gene disabled had very low LDL levels. Different pharmaceutical company started then work on a treatment that could reproduce the same effect. The first  treatments created was made of ripetitive injections of antibodies that blocked the gene.  This new genetic editing technique is a great breakthrough regarding hearth disease because recreate the effect of the mutation find in certain people. 

In my opinion if this gene editing technique could  be administered on larger scale it could make the difference  between preventing and curing hearth diseases. The question at the moment is on the safety of this genetic treatment and on its long lasting effects. If those two aspects of the treatment could be controlled heart disease could become way more easy to fight. 

 3D angiogram scan of a heart with atherosclerosis 

New Research Points to Promise of Gene Therapy for High Cholesterol

 

        Two new gene-editing treatments that target extremely high levels of cholesterol in people genetically predisposed to the condition were found safe and effective in two new studies. One of the treatments, from Verve Therapeutics based in Boston, targets the PCSK9 gene using a gene-editing approach. A tiny change is made to the gene, affecting the gene as an eraser, deleting the gene’s ability to fuel a rise in cholesterol levels. In Verve’s preliminary study, 10 patients received doses that did not make a measurable difference in their LDL levels, however 3 patients were given higher doses and their LDL levels decreased by more than half. Verve’s research was limited to people with the genetic disorder familial hypercholesterolemia. With this condition, cholesterol levels are high from birth and many patients suffer from heart attacks in their 30s or 40s.  The second study demonstrated the possibility of treating high levels of lipoprotein(a) cholesterol. People with this genetic condition of high lipoprotein(a) are at a higher risk of having their arteries clogged because Lp(a) attaches itself to LDL making them stickier and more likely to cause plaque. The study involved 48 patients who were given a drug called lepodisiran, which targets mRNA. In this condition, mRNA tells the body to produce Lp(a) but the drug stops this process. Via the study, the drug was found to be safe with no major side effects but also dramatically lowered Lp(a) levels, decreasing levels by 94% for nearly one year. 

The results presented by these two studies show really exciting, promising results. Even though there are still years of additional research before the FDA would consider approving them, these results show results that could be incredibly beneficial for individuals with high cholesterol levels. The first PCSK9 gene study could theoretically be a one-time treatment that would last an individual their lifetime. The mRNA gene study could also theoretically become a treatment similar to that of a yearly vaccination to treat the disorder. The possibilities created from both these studies could relieve individuals with those disorders of the daily prescriptions and injections, and from the strict diet and exercise. And more importantly, the expected lifespan could increase by a lot with a decrease in other medical risks like expected heart attacks. While these studies on gene therapy have made a big impact on treatments for genetically disposed high cholesterol levels, it also paves the way for a broader look into therapeutic gene therapies for different cardiovascular diseases. 

https://www.usnews.com/news/health-news/articles/2023-11-13/two-new-studies-point-to-the-promise-of-gene-therapy-for-high-cholesterol 

https://www.cdc.gov/genomics/disease/lipoprotein_a.htm 

https://www.cdc.gov/genomics/disease/fh/FH.htm#:~:text=Familial%20hypercholesterolemia%20(FH)%20is%20a,sometimes%20called%20%E2%80%9Cbad%20cholesterol.%E2%80%9D

No More Cholesterol

In an article posted by Julie Steenhuysen on the Reuter's website, it informs that there are studies being done using nanotechnology to permanently edit genes. In "Nanotech, gene editing used to edit cholesterol gene: U.S. study," US researchers are integrating nanotechnology and gene editing techniques, specifically CRISPR.  In my last article I mentioned that a company was going to use a virus-like vehicle to deliver the CRISPR scissors, in this article, researchers are instead inserting chemically-modified CRISPR components into nano-scale fat particles and injecting them into mice, where they eventually make their way to liver cells. Located in these liver cells is the gene of interest, PCSK9- otherwise known as the cholesterol gene. While some drug companies have been able to synthesize drugs that inhibit this mechanism (shown above), many of these drugs are ineffective for patients who suffer from high cholesterol. Researchers now believe that they can get rid of this gene all together so that patients who suffer from atherosclerosis and hypercholesterolaemia can find relief. The same team of researchers are hoping to find other liver-associated diseases that they can possibly treat with their nanotechnology/CRISPR system.

I think that these researchers have an ingenious way of transporting the CRISPR technology into the body. There is a better chance that the body will invite the fat particles instead of unknown virus vehicles which our antibodies can attack. The removal of this gene would mean that no cholesterol proteins are synthesized, even in future filial generations! While this does sound amazing, it also does scare me that genes can be erased so easily. Who decides who gets this power?? There needs to be limitations to who can use this kind of technology. I understand that some researchers are using this technology for scientific reasons, but then there are others who will abuse it till no end. Also, this research makes me think what problems will arise due to the cholesterol gene deletion. Since we evolved with this gene, it has to play a more significant role in our genome in some way or another. Ultimately, I hope this research gives light to cures for other prominent diseases in our society today.


References:

http://www.reuters.com/article/us-health-gene/nanotech-gene-editing-used-to-edit-cholesterol-gene-u-s-study-idUSKBN1DD1ZN

http://www.pharmaceutical-journal.com/news-and-analysis/features/pcsk9-inhibitors-the-next-cholesterol-lowering-blockbusters/20068181.article