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New oral drug lowers cholesterol by 70%

New oral drug lowers cholesterol by 70%

#oral #drug #lowers #cholesterol Welcome to Alaska Green Light Blog, here is the new story we have for you today:

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Cholesterol is a waxy substance found in the fats (lipids) in your blood. While your body needs cholesterol to build healthy cells, too much cholesterol can cause plaque to build up in your arteries and increase your risk of heart attack and stroke.

A team from University Hospitals and Case Western Reserve University has identified a small molecule drug that is effective at reducing cholesterol levels by 70% in animal models.

PCSK9 inhibitors are the second most common type of cholesterol-control medication after statins. These drugs are highly effective at reducing excess cholesterol in the blood, but unlike statins, which can be taken orally, PCSK9 inhibitors must be injected. This can be a barrier to their use for some people.

A small molecule drug that can be taken orally has been developed by researchers at University Hospitals and Case Western Reserve University School of Medicine. In animal models, the drug has been shown to significantly lower PCSK9 levels and reduce cholesterol levels by 70%. These findings, published in the journal Cell Reports, represent a new approach to cholesterol control and may also have implications for cancer treatment.

“Lowering cholesterol is one of the most important therapies we have to prolong life and protect people from heart disease, which is still the leading cause of morbidity and mortality in the western world,” said Jonathan S. Stamler, MD, Senior Author, President, Harrington Discovery Institute at UH, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation, and Professor of Medicine and Biochemistry at UH and Case Western Reserve School of Medicine.

“So far, statins only lower cholesterol levels. This is a class of drugs that we believe would represent a new way to lower cholesterol, a new way to reach PCSK9.”

study results

Central to cholesterol regulation are LDL receptors, which sit on the surface of liver cells and remove cholesterol from the blood, thereby lowering serum levels. PCSK9 in the bloodstream controls the number of LDL receptors by marking them for breakdown. Therefore, agents that inhibit PCSK9 increase the number of LDL receptors that remove cholesterol.

Nitric oxide is a molecule known to help prevent heart attacks by widening blood vessels. In the new study, Stamler and colleagues show that nitric oxide can also target and inhibit PCSK9, thereby lowering cholesterol levels. They identify a small molecule drug that increases PCSK9 nitric oxide inactivation. Mice treated with the drug showed a 70% reduction in “bad” LDL cholesterol.

Beyond cholesterol to cancer

In addition to impacting the domain of cholesterol metabolism, the findings may also have implications for cancer patients, as recent evidence suggests that targeting PCSK9 may improve the effectiveness of cancer immunotherapies.

“PCSK9 not only targets the degradation of LDL receptors, but also mediates the degradation of MHC 1 on lymphocytes, which is used to detect cancer cells,” Stamler said. “PCSK9 effectively prevents your lymphocytes from recognizing cancer cells. So by inhibiting PCSK9, you can improve the body’s cancer surveillance. Maybe one day there will be an opportunity to use these new drugs to address that need.”

Reference: “A multienzyme S-nitrosylation cascade regulates cholesterol homeostasis” by Colin T. Stomberski, Nicholas M. Venetos, Hua-Lin Zhou, Zhaoxia Qian, Bryce R. Collison, Seth J. Field, Richard T. Premont, and Jonathan S. Stamler, October 25, 2022, cell reports.
DOI: 10.1016/j.celrep.2022.111538

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