Key Points:
- A new oral drug that has been shown to lower cholesterol in mice opens new doors for treatment.
- The small-molecule drug reduces PCSK9 levels and lowers cholesterol in animal models by 70%.
- Evidence suggests targeting PCSK9 can also improve the efficacy of cancer immunotherapies.
Researchers at University Hospitals and Case Western Reserve University School of Medicine have discovered a drug class that lowers cholesterol in animal models, opening up a previously unrecognized strategy for managing cholesterol that may also impact cancer treatments.
After statins, the next leading class of medications for managing cholesterol are PCSK9 inhibitors. But, PCSK9 inhibitors can only be administered as shots, creating barriers to their use. Now, researchers have found an orally administered small-molecule drug that reduces PCSK9 levels and lowers cholesterol in animal models by 70%.
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.
In the new study published in Cell Reports, researchers show that nitric oxide can also target and inhibit PCSK9, thus lowering cholesterol. They identified a small molecule drug that functions to increase nitric oxide inactivation of PCSK9. Mice treated with the drug displayed a 70% reduction in LDL “bad” cholesterol.
Additionally, 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 Jonathan Stamler, MD, senior author, professor of medicine and biochemistry at University Hospitals and Case Western Reserve. “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.”
Information provided by University Hospitals.