Schering-Plough finds key to cholesterol-lowering drug.

Schering-Plough finds key to cholesterol-lowering drug.

Researchers at US pharmaceutical company Schering-Plough have identified a protein that plays a major role in cholesterol absorption in humans and may be the main target of Zetia (ezetimibe), its new cholesterol-lowering drug.

’This finding represents an important new discovery which helps explains how the body regulates cholesterol absorption,’ asserts Christie Ballantyne, professor of medicine at Baylor College of Medicine, Houston, US,

In humans, cholesterol is mainly absorbed in the proximal jejunum of the small intestine. The researchers from Schering-Plough knew that ezetimibe acts by inhibiting the uptake of cholesterol by cells known as enterocytes.

To identify which protein might be involved, they searched for genes coding for proteins that possessed features expected in a cholesterol transporter. Only one credible candidate emerged: a gene coding for a protein called Niemann-Pick C1 Like 1 (NPC1L1).

After confirming that NPC1L1 is highly expressed in human enterocyte cells from the proximal jejunum, the researchers created transgenic mice that lacked the gene. While healthy in every other way, these mice absorbed 70 per cent less cholesterol from their diet than normal mice. Furthermore, administering ezetimibe to these mice had no effect, while in normal mice it caused them to absorb 70 per cent less cholesterol.

Jon Evans