High cholesterol is a well-known menace that clogs arteries and raises heart disease risk, but researchers from the University of Barcelona and the University of Oregon have cooked up a new approach that doesn't rely on statins. Instead, they've turned to specialized DNA molecules called polypurine hairpins (PPRHs) to block a protein named PCSK9, which normally prevents cells from hoovering up LDL cholesterol. The result? A 47% drop in cholesterol levels in mice after a single injection, according to a study published in Biochemical Pharmacology.
The team, led by Carles J. Ciudad and Verònica Noé from the University of Barcelona's Faculty of Pharmacy and Food Sciences and the Institute of Nanoscience and Nanotechnology (IN2UB), along with Nathalie Pamir at the University of Oregon, designed two specific PPRHs, HpE9 and HpE12, that bind to the PCSK9 gene and stop it from being transcribed. In liver cells, HpE12 slashed PCSK9 RNA by 74% and protein by 87%. In transgenic mice with the human PCSK9 gene, a single shot of HpE12 cut plasma PCSK9 levels by 50% and cholesterol by 47% on day three. The researchers say this method could avoid the muscle pain and other side effects associated with statins, and it's cheaper and more stable than existing gene-silencing therapies like Inclisiran or monoclonal antibodies. The study was funded by the Spanish Ministry of Science, Innovation and Universities (MICINN) and the National Institutes of Health (NIH). If further tests confirm the results, this could mean a safer, more targeted way to keep your arteries from turning into a plaque museum.