From Lab to Life: Drug Lowers LDL Forever

Source:  depositphotos.com

Cardiovascular diseases (including heart attacks and strokes) cause an estimated 19.2 million to 20.5 million deaths globally each year, making it the leading cause of death worldwide. In the US, cardiovascular disease kills nearly 800,000 Americans a year.  So, rate heart disease as a worse killer than cancer.

Heart attacks occur when plaque forms on veins and arteries supplying blood to and from the heart. Plaque, in turn, is a result of LDL (‘bad’ cholesterol, or low-density lipoprotein; ‘good’ cholesterol is HDL, high-density lipoprotein).

Writing in the New York Times, May 25, Gina Kolata reports that “A single infusion of an experimental gene-editing drug seemed to reduce LDL long-term in a small trial. The results may point to something “curative,” one expert said.  …. In 35 patients, a single infusion of the highest dose of the treatment reduced LDL cholesterol levels by as much as 62 percent. The change has been sustained in a subgroup whose members were treated 18 months ago.”

I and many many others take a statin drug regularly, to lower LDL levels.  Statins work well, and have saved many lives. But, imagine if a one-time infusion could permanently, forever, lower LDL levels!

Here is how scientists * came up with this amazing drug, as clearly explained by Kolata:

• Patel, J., Shah, S., Reddy, A., Prajapati, D., Pandya, A., & Sawhney, S. (2026). Novel Approaches to Lipid Management: Beyond Statins and PCSK9 Inhibitors. Journal of Clinical Medicine Research, 18(3), 121.

“Patients in the trial received an infusion containing a gene editing “machine,” or a tiny molecular factory wrapped in a cloak of fat. The fat-coated particles travel through the blood directly to the liver, where they are taken up by cells that remove the fatty wrapper. The editing machine then crawls along the liver cell’s DNA until it finds its target, a gene called PCSK9. It stops there and erases one DNA letter in the gene, replacing it with another.” The result:  the problematic gene that causes many people to have high LDL levels, despite diet and statins is repaired – permanently.

Gene therapy has been used to cure rare diseases. But it is prohibitively expensive, involving individual treatment of human cells.  This anti-LDL drug is an example of gene therapy, that is incredibly fast, inexpensive and effective. By the way, the use of fat to wrap drugs, protecting them from destruction by the body’s immune system, is well established. The fat wrapping the drug molecule here does double duty – it brings the drug to the liver, whose job it is, among others, to digest fat, thus exposing the drug molecule precisely in the spot where it is needed.

Kudos to these very very clever researchers. If the drug proves safe, in larger-scale trials, it will save millions of lives. The lead author, J. Patel, is from Florida Atlantic University.