Nisha Pandey

Health and Me

Scientists Find New Way To Fight Bad Cholesterol: Could It Offer An Alternative To Statins?

Scientists Find New Way To Fight Bad Cholesterol; Experimental Drug Shows Positive Outcome

Scientists have discovered a previously unknown mechanism that could explain why high cholesterol diet makes it challenging for the liver to remove bad cholesterol from the bloodstream. Researchers have also identified an experimental drug that blocks this process, offering a new method for treating high cholesterol.

The findings are published in the journal Nature by researchers from the University of California San Diego School of Medicine. Their experiments showed that blocking a specific enzyme called cathepsin A (CTSA) helped retain the liver's ability to clear low-density lipoprotein (LDL), commonly known as bad cholesterol.

In mice, inhibiting this enzyme stabilised LDL receptors in liver cells, reducing LDL cholesterol.

"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," said senior author Alan Saltiel, professor of medicine at UC San Diego School of Medicine. "This new discovery explains a critical piece of that puzzle."

The liver plays a key role in regulating cholesterol levels. It uses LDL receptors located on the surface of liver cells to capture LDL <a href="https://www.healthandme.com/health-wellness/coq10-for-statin-related-muscle-pain-what-does-the-evidence-say-article-156412776" data-type="tilCustomLink">cholesterol</a> from the bloodstream.

When fewer of these receptors are available, the liver becomes less efficient at removing LDL cholesterol, allowing it to increase in the bloodstream. The researchers discovered that consuming high amounts of dietary cholesterol activates a protein called Ral. This increases the activity of CTSA, an enzyme that breaks down LDL receptors. 

As these receptors are lost, the liver's ability to clear bad cholesterol declines. When researchers blocked CTSA using a small molecule inhibitor, LDL receptors became more stable and LDL cholesterol levels decreased dramatically in mice.

Also read: <a href="https://www.healthandme.com/health-wellness/recreational-drugs-steroids-birth-control-expert-explains-why-strokes-are-arriving-decades-earlier-article-156428316" data-type="tilCustomLink">Recreational Drugs, Steroids &amp; Birth Control: Expert Explains Why Strokes Are Arriving Decades Earlier</a>

<h2>Experimental Drug That Can Help Lower Cholesterol</h2>

Statins for High Cholesterol Explained: Who Needs Them, Side Effects & Long-Term Use

The discovery has sparked interest as researchers have identified an experimental drug that targets CTSA. The drug was originally developed as a possible treatment option for <a href="https://www.healthandme.com/health-wellness/heart-transplant-in-india-why-thousands-of-patients-may-never-reach-the-waiting-list-article-156353458" data-type="tilCustomLink">heart failure</a>. Although its development for that purpose was discontinued for other reasons, it had already completed a Phase 1 clinical trial, which evaluated its safety in humans.

This previous test could help researchers move towards studying its ability as a cholesterol treatment. However, the drug has not yet been shown to lower LDL cholesterol in humans. 

"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," Saltiel said.

He added, "This new pathway we discovered is completely separate from anything that existing drugs target, so it gives us a new opportunity to fill that gap."

The researchers hope to test the experimental CTSA inhibitor in a Phase 2 clinical trial to determine whether it can safely and effectively lower cholesterol in people. If successful, the approach could offer another option for people who struggle to control LDL cholesterol despite using existing treatments.

Saltiel said, "Luckily, there's an experimental drug sitting on the shelf that's already been shown to be safe in humans."

"We hope to test whether this might be effective by conducting a clinical trial -- which could potentially bring a new treatment option to patients much sooner than would have been expected."

Health Conditions A-Z

health

scientists-find-new-way-to-fight-bad-cholesterol-experimental-drug-shows-positive-outcome

cholesterol

Bad Cholesterol

ldl cholesterol

cathepsin A

CTSA

good cholesterol

nature

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Scientists have discovered a previously unknown mechanism that could explain why high cholesterol diet makes it challenging for the liver to remove bad cholesterol from the bloodstream. Researchers have also identified an experimental drug that blocks this process, offering a new method for treating high cholesterol.The findings are published in the journal Nature by researchers from the University of California San Diego School of Medicine. Their experiments showed that blocking a specific enzyme called cathepsin A (CTSA) helped retain the liver's ability to clear low-density lipoprotein (LDL), commonly known as bad cholesterol.In mice, inhibiting this enzyme stabilised LDL receptors in liver cells, reducing LDL cholesterol."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," said senior author Alan Saltiel, professor of medicine at UC San Diego School of Medicine. "This new discovery explains a critical piece of that puzzle."More About The ExperimentThe liver plays a key role in regulating cholesterol levels. It uses LDL receptors located on the surface of liver cells to capture LDL cholesterol from the bloodstream.When fewer of these receptors are available, the liver becomes less efficient at removing LDL cholesterol, allowing it to increase in the bloodstream. The researchers discovered that consuming high amounts of dietary cholesterol activates a protein called Ral. This increases the activity of CTSA, an enzyme that breaks down LDL receptors. As these receptors are lost, the liver's ability to clear bad cholesterol declines. When researchers blocked CTSA using a small molecule inhibitor, LDL receptors became more stable and LDL cholesterol levels decreased dramatically in mice.Also read: Recreational Drugs, Steroids & Birth Control: Expert Explains Why Strokes Are Arriving Decades EarlierExperimental Drug That Can Help Lower Cholesterol         The discovery has sparked interest as researchers have identified an experimental drug that targets CTSA. The drug was originally developed as a possible treatment option for heart failure. Although its development for that purpose was discontinued for other reasons, it had already completed a Phase 1 clinical trial, which evaluated its safety in humans.This previous test could help researchers move towards studying its ability as a cholesterol treatment. However, the drug has not yet been shown to lower LDL cholesterol in humans. "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," Saltiel said.He added, "This new pathway we discovered is completely separate from anything that existing drugs target, so it gives us a new opportunity to fill that gap."The researchers hope to test the experimental CTSA inhibitor in a Phase 2 clinical trial to determine whether it can safely and effectively lower cholesterol in people. If successful, the approach could offer another option for people who struggle to control LDL cholesterol despite using existing treatments.Saltiel said, "Luckily, there's an experimental drug sitting on the shelf that's already been shown to be safe in humans.""We hope to test whether this might be effective by conducting a clinical trial -- which could potentially bring a new treatment option to patients much sooner than would have been expected."