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NEW YORK DAWN™ > Blog > Health > New therapeutic technique designed to assist decrease levels of cholesterol
New therapeutic technique designed to assist decrease levels of cholesterol
Health

New therapeutic technique designed to assist decrease levels of cholesterol

Last updated: June 11, 2025 5:18 pm
Editorial Board Published June 11, 2025
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A examine led by the College of Barcelona and the College of Oregon presents a brand new methodology—primarily based on molecules often known as polypurine hairpins—able to appearing on the PCSK9 protein, a recognized therapeutic goal for lowering blood ldl cholesterol. Credit score: Biochemical Pharmacology

When the quantity of ldl cholesterol within the blood is simply too excessive, hypercholesterolemia can develop, inflicting critical harm to the arteries and cardiovascular well being. Now, a examine led by the College of Barcelona and the College of Oregon presents a brand new therapeutic instrument able to regulating blood levels of cholesterol and thus opening up new views within the struggle towards atherosclerosis attributable to the buildup of lipid plaques within the artery partitions.

Particularly, the workforce has designed a method to inhibit the expression of PCSK9, a protein that performs a decisive function in modulating plasma ranges of low-density lipoprotein ldl cholesterol (LDL-C). The brand new technique, primarily based on using molecules often known as polypurine hairpins (PPRH), facilitates the uptake of ldl cholesterol by cells and prevents it from accumulating within the arteries with out inflicting the unwanted effects of the most typical statin-based remedy.

The paper, printed within the journal Biochemical Pharmacology, was led by specialists Carles J. Ciudad and Verònica Noé, professors on the UB’s School of Pharmacy and Meals Sciences and the Institute of Nanoscience and Nanotechnology (IN2UB), in collaboration with Nathalie Pamir, from the College of Oregon in Portland (United States).

Polypurine hairpins for PCSK9 expression inhibition

PCSK9 (protein convertase subtilisin/kexin sort 9) is an enzyme that has emerged during the last decade as a therapeutic goal for lowering heart problems and enhancing lipid metabolism. This protein binds selectively and competitively to the mobile receptor itself. Thus, PCSK9 reduces the variety of accessible LDL receptors on cells, which will increase the extent of LDL-bound ldl cholesterol circulating within the blood plasma and in the end causes hypercholesterolemia.

The brand new methodology is predicated on the power of polypurine hairpins (PPRHs) to particularly cease gene transcription.

On this case, PPRHs can inhibit the expression of the PCSK9 gene, thereby growing LDLR receptor ranges and selling ldl cholesterol uptake inside cells. Because of this, circulating levels of cholesterol and the chance of atherosclerosis lower.

PPRHs are oligonucleotides, easy single-stranded DNA molecules which have a excessive affinity for particular DNA and in addition RNA sequences. The examine reveals for the primary time how polypurine hairpins—HpE9 and HpE12—lower PCSK9 RNA and protein, and enhance LDLR ranges.

“Specifically, one of the arms of each chain of the HpE9 and HpE12 polypurines binds specifically to polypyrimidine sequences of exons 9 and 12 of PCSK9, respectively, via Watson-Crick bonds,” notes Professor Carles J. Ciudad, from the Division of Biochemistry and Physiology. This binding inhibits gene transcription and the motion of RNA polymerase or the binding of transcription components.

The brand new therapeutic approach has been validated in vivo in transgenic mice expressing the human PCSK9 gene. “The results show that both HpE9 and HpE12 are highly effective in HepG2 cells. HpE12 decreases PCSK9 RNA levels by 74% and protein levels by 87%. In the case of transgenic mice, a single injection of HpE12 reduces plasma PCSK9 levels by 50% and cholesterol levels by 47% on the third day,” says Professor Noé.

Therapeutic oligonucleotides as a substitute for statins

Since PCSK9 was outlined as a big goal in plasma cholesterol-lowering remedy, a number of therapeutic approaches have been designed to decrease or block its motion. For instance, gene silencing with siRNAs, antisense oligonucleotides or the CRISPR approach. Specifically, Inclisiran, an siRNA agent towards PCSK9, and the monoclonal antibodies akin to evolocumab and alirocumab stand out.

“PPRHs, especially HpE12, are therapeutic oligonucleotides with many advantages, including low cost of synthesis, stability and lack of immunogenicity. In addition, such a PPRH-based approach against PCSK9 would not lead to side effects such as the myopathies associated with statin therapy,” the specialists conclude.

Extra info:
Ester López-Aguilar et al, Inhibition of PCSK9 with polypurine reverse hoogsteen hairpins: A novel gene remedy method, Biochemical Pharmacology (2025). DOI: 10.1016/j.bcp.2025.116976

Offered by
College of Barcelona

Quotation:
New therapeutic technique designed to assist decrease levels of cholesterol (2025, June 11)
retrieved 11 June 2025
from https://medicalxpress.com/information/2025-06-therapeutic-strategy-cholesterol.html

This doc is topic to copyright. Aside from any truthful dealing for the aim of personal examine or analysis, no
half could also be reproduced with out the written permission. The content material is supplied for info functions solely.

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