CLEVELAND — Do you have high cholesterol? A new health study from teams at University Hospitals and Case Western Reserve University School of Medicine has found “an orally administered small-molecule drug that reduces PCSK9 levels and lowers cholesterol in animal models by 70%.”
Details of the study were released Thursday morning.
“Statins only lower cholesterol so far,” an official associated with the study said in a press release. “This is a drug class that we think would represent a new way to lower cholesterol, a new way to hit PCSK9.”
Study findings
Here’s what UH and Case Western officials are saying…
Central to cholesterol regulation are LDL receptors, which sit at 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 degradation. Therefore, agents that inhibit PCSK9 increase the number of LDL receptors that remove cholesterol.
Nitric oxide is a molecule that is known to prevent heart attacks by dilating blood vessels. In the new study, Stamler and colleagues show that nitric oxide can also target and inhibit PCSK9, thus lowering cholesterol. They identify a small molecule drug that functions to increase nitric oxide inactivation of PCSK9. Mice treated with the drug display a 70% reduction in LDL “bad” cholesterol.
Beyond cholesterol to cancer
In addition to impacting the field of cholesterol metabolism, the findings may impact patients with cancer, as emerging evidence suggests targeting PCSK9 can improve the efficacy of cancer immunotherapies.
“PCSK9 not only targets LDL receptors for degradation, it also mediates the degradation of MHC 1 on lymphocytes, which is used for recognition of cancer cells” said Stamler. “PCSK9 is effectively preventing your lymphocytes from recognizing cancer cells. So, if you inhibit PCSK9, you can boost the body’s cancer surveillance. There may be an opportunity one day to apply these new drugs to that need.”
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Editor's note: Video in the player above was originally published in an unrelated story on Nov. 16, 2022.
