High levels of cholesterol in the bloodstream can lead to hypercholesterolemia, a condition that damages arteries and raises the risk of heart disease. Researchers from the University of Barcelona and the University of Oregon have developed an innovative approach to controlling cholesterol levels, offering a new potential way to combat atherosclerosis — the buildup of fatty plaques in artery walls.

Targeting the PCSK9 Protein

The research team focused on PCSK9 (protein convertase subtilisin/kexin type 9), a protein that plays a central role in regulating levels of low-density lipoprotein cholesterol (LDL-C), often called “bad” cholesterol. They designed a method to block the production of this protein using specialized DNA-based molecules known as polypurine hairpins (PPRH).

By suppressing PCSK9, the treatment helps cells absorb more cholesterol, reducing the amount circulating in the blood and limiting buildup in the arteries. Importantly, this approach may avoid the side effects commonly linked to statin medications.

The findings were published in the journal Biochemical Pharmacology.

How It Works

PCSK9 attaches to LDL receptors on cells, limiting their ability to remove cholesterol from the bloodstream. When PCSK9 levels are high, fewer receptors are available, causing LDL cholesterol to accumulate in the blood.

Polypurine hairpins (PPRHs) are short strands of DNA that can bind very precisely to specific DNA or RNA sequences and block gene activity. In this study, the PPRHs prevent the PCSK9 gene from being transcribed, leading to increased LDLR receptor levels and improving the body’s ability to pull cholesterol out of circulation.

The study describes for the first time how two specific PPRHs — HpE9 and HpE12 — reduce both PCSK9 RNA and protein levels while boosting LDL receptor levels.

“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 Department of Biochemistry and Physiology at the University of Barcelona.

Significant Experimental Results

The researchers tested the therapy in laboratory-grown liver cells and in transgenic mice carrying the human PCSK9 gene. The results were striking.

“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,” said Professor Verònica Noé from the University of Barcelona’s Faculty of Pharmacy and Food Sciences.

A Potential Statin Alternative

PCSK9 has become a major target for cholesterol-lowering therapies in recent years. Several approaches have been developed to block its effects, including siRNAs, antisense oligonucleotides, and CRISPR-based methods. Existing treatments such as Inclisiran (an siRNA therapy) and monoclonal antibodies like evolocumab and alirocumab are already in clinical use.

However, PPRHs may offer unique advantages. “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 experts conclude.

If confirmed in further studies, this new strategy could provide a safer and more targeted way to lower cholesterol and reduce the risk of heart disease.

Source: ScienceDaily, Biochemical Pharmacology

On April 28, 2026, the U.S. Food and Drug Administration approved Otarmeni (lunsotogene parvec-cwha), the world’s first dual adeno-associated virus (AAV) vector-based gene therapy for treating severe-to-profound sensorineural hearing loss associated with biallelic OTOF gene variants. The therapy was developed by Regeneron Pharmaceuticals.

The approval marks several milestones: it was granted just 61 days after the Biologics License Application (BLA) was filed, tying for the fastest BLA approval in modern FDA history. It is also the sixth product approved under the Commissioner’s National Priority Voucher (CNPV) pilot program and the first gene therapy product to receive approval under the program.

Genetic mutations cause approximately half of all congenital hearing loss. OTOF gene variants account for 2% to 8% of inherited, non-syndromic cases. Patients with two non-functional copies of the gene cannot produce otoferlin, a protein essential for sound signal transmission. Prior to this approval, no disease-modifying treatments existed for OTOF-related deafness.

Otarmeni is a one-time biologic-device combination product administered surgically as a single dose per ear into the cochlea. It delivers a functional copy of the OTOF gene to inner hair cells, restoring otoferlin production and auditory signaling.

In a clinical trial involving 24 patients aged 10 months to 16 years, 80% of the 20 evaluable patients (16 individuals) experienced improved hearing — an outcome not expected in the natural history of the disease without intervention.

FDA Commissioner Marty Makary, M.D., M.P.H., said: “Today’s approval is a significant milestone in the treatment of genetic hearing loss. Through the national priority voucher pilot program, we are accelerating therapies for rare diseases with unmet medical needs while proving we can successfully review even the most complex submissions — such as novel dual vector gene therapies and combination products requiring coordination across multiple offices and centers — in significantly shortened timeframes.”

Common side effects included middle ear infection, nausea, dizziness, and procedural pain. The therapy has received orphan drug, rare pediatric disease, fast track, and regenerative medicine advanced therapy (RMAT) designations.

Regeneron will continue to collect data on the durability of hearing improvement and verification of treatment effects on clinical measures of speech development and quality of life ahead of the FDA’s public meeting on the CNPV program scheduled for June 4.

Source: FDA, New England Journal of Medicine