Breaking: New Hope in the Fight Against Atherosclerosis – Innovative PCSK9 Inhibition Strategy
A groundbreaking study, published in Biochemical Pharmacology, indicates that a collaborative team from the University of Barcelona and the University of Oregon has designed a novel therapeutic approach to combat atherosclerosis. This disease, caused by the accumulation of lipid plaques in arterial walls, poses significant health risks and is a leading cause of heart disease. The comprehensive research builds on innovative methods to inhibit the expression of the PCSK9 protein, offering a promising alternative to conventional statin medications.
Innovative Approach Using Anti-PCSK9 Oligonucleotides
The study leverages the use of polyamine conjugates (PPRCs) to inhibit the expression of the PCSK9 protein. This mechanism ensures that cells efficiently capture cholesterol, preventing its buildup in arteries and circumventing the side effects commonly associated with statin-based medications. The cornerstone of this method is increasing levels of the low-density lipoprotein receptor (LDLR), which significantly enhances cholesterol uptake in cells, thus reducing its circulation and minimizing the risk of atherosclerosis.
Significant Findings and Collaboration
The research received vital contributions from Nathalie Pamir at the Knight Cardiovascular Institute of Oregon Health and Science University and was supported by grants from the Ministry of Science, Innovation and Universities (MICINN) and the National Institutes of Health (NIH) in the United States. Senior researchers like Carles J. Cor CDUH of the University of Barcelona and Verónica Noah from the University of Oregon outlined the effectiveness of PPRCs in both cell and mouse models.
Prof. Cor explained that the polypurine sequences (HPE9 and HPE12) specifically target exons 9 and 12 of the PCSK9 gene, inhibiting its transcription and RNA polymerase activity. The findings showcased that HPE12, in particular, substantially decreased PCSK9 RNA levels by 74% and protein levels by 87% in human liver cells (HEPG2). Additionally, a single injection of HPE12 reduced plasma PCSK9 levels by 50% and cholesterol levels by 47% in transgenic mice within three days.
Emerging Therapeutics
This research expands current therapeutic horizons by exploring other techniques like RNA interference (siRNA), antisense oligonucleotides, and CRISPR technology to counteract PCSK9’s effects. advantages include stability, minimal immunogenicity, and cost-effectiveness. Notably, this methodology avoids myopathies associated with statins, offering a safer profile.
The future implications of this discovery could lead to more tailored and effective treatments, paving the way for improved patient outcomes. For more detailed updates and insights into this ongoing research, stay tuned to Archyde.
