New Cholesterol Pathway Found in Mice, Human Trial Possible

Researchers at UC San Diego School of Medicine have identified a previously unknown biological pathway that may explain why high cholesterol diets gradually weaken the liver's ability to clear LDL cholesterol from the blood, according to a University of California San Diego release.

In experiments with mice and human cells, the team found that dietary cholesterol activates a protein called Ral, which triggers a chain of events involving an enzyme known as cathepsin A, or CTSA. This process reduces the number of LDL receptors on liver cells, the docking stations that pull cholesterol out of circulation. When researchers blocked CTSA with a small molecule inhibitor, LDL receptors became more stable and LDL cholesterol dropped sharply in mice.

What makes this notable is that an experimental CTSA inhibitor already exists. It was originally developed for heart failure and completed a Phase 1 human safety trial before that program was discontinued for unrelated reasons. According to the researchers, this earlier testing could allow the compound to move more quickly into a Phase 2 trial evaluating it specifically for cholesterol lowering.

It's worth stressing that this pathway is distinct from the ones targeted by statins and PCSK9 inhibitors, which could matter for people who do not respond well to current options. Still, the drug has not been shown to lower cholesterol in humans, and this research remains at an early, preclinical stage.

This article is for education only. It is not medical advice. Compounds discussed here are sold for research purposes. Talk to a licensed clinician before making health decisions.