New Drugs to Clear up Arteries

University of Pennsylvania scientists are conducting research on a new drug designed to clear up arteries and thus, reduce heart disease. The University of Pennsylvania hospital has enrolled volunteers for a trial of the drug D-4F, which is one of the several pioneering methods currently tested in the drug industry.

D-4F is a synthetic version of the protein called apoA-1 Milano, to be sold by Pfizer, the first drug known to reduce the amount of artery-clogging plaque. This new type of drugs aims either to raise the HDL ("good cholesterol") levels in the blood or to improve the effectiveness of HDL. This is because HDL, unlike "bad cholesterol" (LDL), does not create fatty deposits on the artery walls, on the contrary, it

hauls fat from the artery wall to the liver for excretion. It has been shown that people who have high levels of HDL also have cleaner arteries and thus, a decreased risk of cardiovascular disease.

Up until recently, the only ways to increase HDL levels were exercise and high doses of the vitamin niacin. Niacin, however, has side-effects that some patients do not tolerate. Now, there are more than half a dozen ongoing trials competing with one another to fill the treatment gap. Pfizer plans to spend $800 million to develop and test a HDL boosting drug called torceptrapib. Separately, Pfizer is working on an easier-to-make synthetic version of the apoA-1 Milano as well. Roche's drug, code-named JTT-705 is in an earlier stage of testing, while Merck is working on reducing the side effects of niacin. PPAR and LXR agonists are another two drugs currently on trial which researchers hope will successfully unclog arteries.

The University of Pennsylvania trial currently involves 50 patients with heart disease or diabetes. D-4F, made by Bruin Pharmaceuticals and licensed to Novartis, is easier to make than standard apoA-1 or apoA-1 Milano, and is cleverly designed as a mirror image of the natural apoA-1. This way, the digestive tract does not recognize it as a protein, the result being that it can be administered orally, unlike other versions of apoA-1 that must be given intravenously.

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