Experimental gene therapy targets protein to lower bad cholesterol - Sarmad
Preliminary trial results have shown that an experimental gene therapy approach can lower blood levels of bad cholesterol by targeting a protein linked to the regulation of low-density lipoprotein (LDL) levels, potentially paving the way for new methods to control high cholesterol.
According to Sputnik on Sunday, researchers from the University of Barcelona and the University of Oregon developed this approach using short DNA molecules known as “poly-purine repressor” (PPR) pins, with the aim of reducing the production of the PCSK9 protein and increasing the number of LDLR receptors, which help liver cells remove bad cholesterol from the bloodstream. The study’s findings were published in the journal Biochemical Pharmacology.
The researchers tested two molecules of this technology, HpE9 and HpE12, and laboratory experiments showed that both contributed to lowering levels of RNA and proteins associated with PCSK9, alongside an increase in LDLR receptor levels.
HpE12 proved to be the most effective, reducing PCSK9-related RNA levels by 74 percent and protein levels by 87 percent in human liver cells during laboratory trials.
The researchers also tested the approach on genetically modified mice carrying the human PCSK9 gene. The results showed that a single injection of HpE12 led to a 50 percent reduction in PCSK9 levels in blood plasma by the third day of the experiment, while cholesterol levels dropped by 47 percent.
The researchers explained that reducing PCSK9 production can increase the number of LDLR receptors on the surface of liver cells, enhancing their ability to capture and eliminate bad cholesterol from the bloodstream.
They noted that the results are still in the early experimental stages, as tests so far have been limited to human cells in vitro and mouse models. The safety and efficacy of the approach in humans cannot be determined until further studies are conducted.
The findings suggest the potential for developing new therapeutic approaches targeting PCSK9 to help lower bad cholesterol levels. However, transitioning to clinical use requires additional studies to evaluate long-term safety and efficacy.
