Summary
UCLA scientists have identified a novel regulator of cholesterol homeostasis. This regulator can be targeted for drug development to treat hypercholesterolemia and cardiac disease.
Background
Hypercholesterolemia, or high cholesterol, can contribute to a number of diseases, and in particular, elevated levels of low-density lipoprotein (LDL) cholesterol is known to be a major risk factor for the development of cardiovascular disease. Current treatments include lifestyle changes, such as increased exercise, weight loss, healthier eating, and prescription medication, which in most cases involves the use of statins. Despite their widespread use, statins reduce LDL by only 30-50%. Additionally, their use results in several common side effects including muscle pain, nausea, diarrhea, or constipation. In rare cases, statins may cause liver damage or life-threatening rhabdomyolysis. Therefore, alternatives, or additives to statin treatment would prove beneficial in treating hypercholesterolemia.
Innovation
Low-density lipoprotein receptor (LDLR) binds LDL particles and removes them from blood. Researchers at UCLA have identified a protein as a novel regulator of cholesterol homeostasis. Adenoviral-mediated hepatic expression of this novel regulator results in severely diminished LDLR levels, which leads to increased LDL and total cholesterol. A domain in this protein has been identified as critically important in its ability to regulate LDLR levels and lower LDL. Thus, development of methods that inhibit its activity can form the basis for a new class of drugs for treating hypercholesterolemia and cardiac disease.
Applications
- Target this cholesterol regulator for development of genetic methods or chemicals to treat hypercholesterolemia and cardiac disease
- Methods developed to regulate its activity can be used as alternatives, or additives to statin treatment
Advantages
- Novel therapeutic target regulates hepatic LDLR levels independently of the cholesterol biosynthetic pathway
- Alternative to statins mechanism of action
State of Development
This protein was identified as an in-vivo regulator of hepatic levels of LDLR. Mouse model developed.