Researchers discover new drug to lower cholesterol

An oral small-molecule medication that decreases PCSK9 levels and cholesterol in animal models by 70 per cent.
Representative image
Representative imageANI

CLEVELAND (US): PCSK9 inhibitors are the second most used family of drugs for lowering cholesterol after statins.

These extremely efficient medications aid in the removal of excess cholesterol from the blood, but unlike statins, which can be taken orally, PCSK9 inhibitors can only be given intravenously, posing limitations to their administration.

An oral small-molecule medication that decreases PCSK9 levels and cholesterol in animal models by 70 per cent is now described in a new study by researchers at University Hospitals (UH) and Case Western Reserve University School of Medicine.

The research, which was published in Cell Reports, reveals a new way to control cholesterol that could possibly have an effect on cancer treatments.

"Cholesterol lowering is one of the most important therapies we have to prolong life and protect people from heart disease, which is still the number one 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.

"Statins only lower cholesterol so far. This is a drug class that we think would represent a new way to lower cholesterol, a new way to hit PCSK9."

Study Findings

LDL receptors, which are found on the surface of liver cells and remove cholesterol from the blood, are essential for controlling serum cholesterol levels.

By designating them for destruction, PCSK9 in the bloodstream regulates the number of LDL receptors. The quantity of LDL receptors that remove cholesterol is thereby increased by PCSK9 inhibitors.

By widening blood arteries, the chemical nitric oxide is known to prevent heart attacks. Nitric oxide can target and inhibit PCSK9, which lowers cholesterol, as demonstrated in the latest work by Stamler and colleagues.

They discover a small-molecule medication that boosts PCSK9 nitric oxide inactivation. The drug-treated mice show a 70 per cent decrease in LDL "bad" cholesterol.

Beyond Cholesterol to Cancer

The findings may have an impact on patients with cancer as well as the field of cholesterol metabolism because new research indicates that targeting PCSK9 can boost the effectiveness of cancer immunotherapies.

"PCSK9 not only targets LDL receptors for degradation, but 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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