TL;DR
Get workout gear delivered free with Prime
- Fast, free delivery on millions of items
- Prime Video, Amazon Music and more included
- Member-only deals all year
UC San Diego researchers reported a pathway in which dietary cholesterol activates Ral and the enzyme CTSA, reducing liver LDL receptors in experiments with mice and human cells. Blocking CTSA lowered circulating LDL in mice, but the candidate drug has not been shown to lower cholesterol in people; researchers say a clinical trial is needed.
Researchers at the University of California San Diego School of Medicine have identified a biological pathway that may help explain how a high-cholesterol diet reduces the liver’s ability to remove LDL cholesterol. In experiments with mice and human cells, blocking the enzyme CTSA stabilized LDL receptors and lowered circulating LDL in mice; whether the approach works in people remains unknown.
The study, published in Nature, describes a chain of events involving a protein called Ral and an enzyme called cathepsin A, or CTSA. The researchers report that dietary cholesterol activates Ral, leading to processes that reduce the number of LDL receptors on liver cells. Those receptors help capture LDL from the bloodstream so the liver can process it.
When the team used a small-molecule inhibitor to block CTSA, LDL receptors became more stable and circulating LDL levels dropped in mice. The findings are from preclinical experiments; the supplied report does not provide the size of the LDL reduction, the length of the experiments, or evidence that the effect occurs in people.
The researchers also point to an experimental CTSA-inhibiting drug that was developed for heart failure and previously completed a Phase 1 safety trial in humans. Its development program was discontinued for strategic reasons, according to the report. The drug has not been shown to lower cholesterol in people, and Phase 1 safety testing does not establish that it is effective or safe for this new use.
A Different Target for LDL Reduction
The proposed pathway could offer researchers a new target for cholesterol treatment. The study authors say it differs from pathways targeted by current treatments, including statins and PCSK9 inhibitors, which help maintain or increase the number of LDL receptors available to clear cholesterol. That difference could matter for patients whose LDL remains high despite existing medicines or who have difficulty taking them, though the study does not show that this candidate would help those patients.
The work also connects a diet-related effect to a specific biological process: fewer liver LDL receptors could mean less capacity to remove LDL from circulation. But the experiments do not establish how much this mechanism contributes to high cholesterol in people, or whether blocking it would lead to meaningful health benefits. Any potential treatment would need clinical testing for both effectiveness and risks.
Products Worth Considering
Withings BPM Connect Wi-Fi and Bluetooth Blood Pressure Monitor
Fitbit Versa 2 Health and Fitness Smartwatch with Heart Rate, Alexa, Music, Sleep and Swim Tracking
Coway Mighty AP-1512HH(W) Air Purifier, White
As an affiliate, we earn on qualifying purchases.
How the Liver Clears LDL
The liver helps regulate cholesterol in the blood. Its cells use LDL receptors to take LDL particles out of circulation for processing. Treatments such as statins and PCSK9 inhibitors affect the availability or function of these receptors, although they work through mechanisms different from the one described in this study.
According to senior author Alan Saltiel, the researchers set out to understand why a high-cholesterol diet can weaken the liver’s ability to clear cholesterol. The team’s findings add a proposed Ral–CTSA pathway to that picture. The report says the candidate drug had already undergone human safety testing for a different potential use, which may provide a starting point for further research, not proof of benefit against high cholesterol.
“This new discovery explains a critical piece of that puzzle.”
— Alan Saltiel, senior author and professor of medicine at UC San Diego School of Medicine
Human Benefits Remain Untested
The supplied report does not say that a trial for high cholesterol has begun. It also gives no clinical evidence that the CTSA inhibitor lowers LDL in people. The earlier Phase 1 trial assessed safety in humans for a potential heart-failure treatment; it cannot establish the drug’s effectiveness or safety for cholesterol management.
Further questions include whether the mouse findings translate to people, what dose might be appropriate, how the drug would compare with existing medicines, and what side effects could emerge with longer use. The report does not specify a trial start date, enrollment plan, or timeline for results.
Clinical Testing Is the Next Step
Saltiel and colleagues say they hope to test whether the existing CTSA inhibitor can lower cholesterol in a clinical trial. The report suggests the candidate could potentially move toward Phase 2 testing, but it does not confirm that a trial has been approved, funded, or started.
Before the approach could become a treatment option, researchers would need to test its effect on LDL in patients and assess safety for this use. Until such results are available, people should not treat the findings as a reason to change prescribed cholesterol medication or diet plans; treatment decisions should be made with a health professional.
Key Questions
What pathway did the researchers identify?
The study links activation of Ral by dietary cholesterol to a process involving CTSA that reduces LDL receptors on liver cells. The findings come from experiments with mice and human cells.
Did blocking CTSA lower cholesterol in people?
No human cholesterol-lowering result is reported. Blocking CTSA stabilized receptors and lowered circulating LDL in mice; the effect in people remains untested.
Has the drug already been tested in humans?
The report says an experimental CTSA inhibitor completed a Phase 1 safety trial when being developed for heart failure. That does not show it is effective against high cholesterol or establish safety for that use.
When could the treatment become available?
No availability date is given. Researchers say they hope to test the approach in a clinical trial, but the report does not confirm that a cholesterol trial has started.
Source: sciencedaily.com
