Scientists at the University of California San Diego School of Medicine have uncovered a previously hidden biological mechanism that could lead to a new treatment for high cholesterol, offering an alternative to statins. The study, published in the journal Nature, reveals how elevated cholesterol dismantles the liver's natural defenses against harmful LDL or 'bad' cholesterol, and identifies a drug candidate already proven safe in humans.
How High Cholesterol Undermines the Liver
The research team discovered that a high-cholesterol diet gradually reduces the liver's ability to clear cholesterol from the bloodstream. Study senior author Professor Alan Saltiel explained: 'We've known for a long time that a high-cholesterol diet reduces the liver's ability to clear cholesterol from the blood, but we didn't fully understand why.' The team found that this occurs through a biological mechanism that was not previously understood.
Key Enzyme Identified: Cathepsin A
Blocking a specific enzyme called cathepsin A was shown to 'dramatically lower' circulating LDL cholesterol in mice. According to Prof Saltiel, 'There's still a real need for new cholesterol-lowering options, since some people can't get to safe levels even with the drugs we have now.' The discovery could bring new treatment options to patients much sooner than expected.
Existing Drug Candidate
An experimental drug that targets this pathway has already progressed through early safety trials for heart failure treatment. Prof Saltiel noted: 'Luckily, there's an experimental drug sitting on the shelf that's already been shown to be safe in humans.' This could accelerate the availability of a new treatment option for those who struggle with current medications like Atorvastatin and Simvastatin.
Impact and Future Outlook
The breakthrough offers hope to millions who cannot achieve safe cholesterol levels with existing drugs. The researchers believe that this new approach could provide an effective alternative to statins, which are commonly prescribed but not always tolerated or effective for all patients.
