SNU professor investigates new anti-cholesterol medicine

CAP-inhibiting medicine to undergo Phase 1 trial

Targeting indication treating fatty liver and cancer

김효수 교수

Researchers in Korea are onto developing a next generation anti-cholesterol medicine.

 

Pharmaceutical industry reported on Jan.

 

7, a team of Seoul National University researchers led by Professor Kim Hyo-soo is preparing a Phase 1 clinical study on candidate medicine inhibiting cyclase-associated protein 1 (CAP1).

 

Previously, Seoul National University Hospital’s Research-driven Hospital Project—Inflammation/ Metabolism Unit Program led by Professor Kim Hyo-soo and Professor Jang Hyun-duk discovered CAP1 protein essential for protein convertase subtilisin/kexin type-9 (PCSK9) to destroy low-density lipoprotein (LDL)-receptor and identified the mechanism.

 

LDL-cholesterol, when combined with LDL-receptor on the surface of hepatocytes, enters into the hepatocyte through a pathway called clathrin.

 

Then the LDL-cholesterol is broken down, while LDL-receptor moves back to the cell surface and is reused.

 

After then, CAP1 carries PCSK9 combined with LDL-receptor to an intracellular pathway, caveolin, where LDL-receptor is broken down by lysosome without getting reused.

 

In short, PCSK9 is essential for CAP1 to break down LDL-receptor.

 

Interestingly, CAP can be found in every organ of a human body, which means CAP1-inhibiting mechanism could be effective not only for lowering cholesterol level but also for other disease.

 

In fact, the CAP1-inhibitor, currently under investigation by Professor Kim’s team, is targeting for indication on treating fatty liver and cancer.

 

Professor Kim Hyo-soo stated, “With the six-year-long research, we have confirmed possibility of the investigational medicine, and we are planning for a Phase 1 trial on the medicine.

 

Although PCKS9-inhibitor has been commercialized and demonstrated effectiveness, CAP-inhibitor could be another treatment option.” The team has already conducted a study with CAP1-inactivated mice.

 

The outcome found the mice lacking CAP1 had hepatocyte surface with increased LDL-receptor and had significantly lower the level of LDL-cholesterol level in its blood.

 

Also when intentionally breaking down LDL-receptor in liver of mice injected with PCSK9 antibody, the symptom of degraded LDL-receptor has been improved noticeably in mice without CAP1.

 

Moreover, the research team analyzed PCSK9 gene mutation in people with considerably low LDL-cholesterol and found mutated PCSK9 could not properly bind with CAP1 to be functional.