Gene Editing to Lower Cholesterol
Scientists have altered the PCSK9 gene in monkeys to reduce gene function and lower bad cholesterol levels by 60 to 90 percent. A single treatment achieved these levels for 8 months. LDL-cholesterol receptors on the surface of liver cells are the main way humans control bad cholesterol levels. The PCSK9 gene makes a protein that destroys these receptors. Fewer LDL receptors results in higher cholesterol levels. This is the way familial hypercholesterolemia works. (Very high cholesterol that runs in families) Families with extremely high cholesterol levels have PCSK9 genes that are overactive. Drugs called PCSK9 inhibitors block that protein and can produce very low cholesterol levels in these patients. Medications like Repatha in this category cost about $500 a month. The medications produce the same effect in a different way, and they are available for human use now.
Gene therapy for arterial disease is not likely to be a magic bullet. LDL cholesterol levels are a potent risk factor for cardiovascular disease, but that is not the whole story. PCSK9 inhibitors like Repatha lower LDL or bad cholesterol just as effectively as the gene treatment. We know very precisely what this medication does. Added to statin treatment, it only lowers the risk of a heart attack another 15-20%. In diabetic patients, statin treatment lowers the risk of major cardiovascular events by 55%. That is a huge difference. Cholesterol is not the whole story in heart artery disease. Many patients have heart attacks with normal cholesterol levels.
Statins also inhibit a very specific gene involved in cholesterol synthesis. Statins prevent heart attack even in patients with normal cholesterol levels. This gene also increases oxidant production which accelerates aging and chronic disease development independent of the effect on increasing LDL or bad cholesterol synthesis. It also promotes inflammation. Statin reduce inflammation and oxidant production before LDL cholesterol levels go down. A single dose of a statin reduces heart muscle injury in an experimentally induced heart attack in a lab animal by half before it changes the cholesterol level. Statins lower the risk of heart attack more than other drugs that achieve the same cholesterol level. Additionally, numerous other genes for hormonal factors and tobacco smoke contribute to arterial disease development. Stopping smoking and blocking the impact of these factors is also necessary. Lisinopril and losartan for high blood pressure, metformin and empagliflozin for diabetes, and statins for cholesterol are synergistic in reducing vascular risk. Instead of reducing heart attack risk by 15 to 20 percent, these interventions together produce a 4-fold reduction. Maximal heart attack risk reduction requires a comprehensive solution combining all these factors to improve health and reduce cost. That is why optimal medical treatment is important. We already have very precise ways to avoid heart attacks. Please subscribe to stay current on the new science. Subscriptions are free.