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Test Achieves Cholesterol Breakthrough

November 5, 2003

CHICAGO (AP) -- An experimental treatment that seems to work like "liquid Drano" for clogged arteries stems from remarkably healthy villagers in northern Italy found to have paradoxically lousy cholesterol levels.

Scientists think a genetic mutation in HDL cholesterol explains the villagers' good health. And using a synthetic version of that substance, they were able to reduce fatty artery plaque in just six weeks in patients with heart disease.

Larger and longer studies are needed to determine if the experimental treatment will translate into fewer deaths, but the early results are promising, said Dr. Daniel Rader, director of preventive cardiology at the University of Pennsylvania School of Medicine.

The surprisingly quick results, though preliminary, shatter a long-standing belief that heart disease is a slow-progressing disease that takes a long time to undo, said Rader, who wrote an editorial accompanying the study in Wednesday's Journal of the American Medical Association.

"This is clearly on the level of a breakthrough that will have far-reaching implications," potentially pointing the way toward a rapid treatment for fatty buildups, said Dr. Bryan Brewer, chief of molecular diseases at the National Heart, Lung and Blood Institute.

The treatment involved infusions of a laboratory-produced version of the mutated HDL, the good cholesterol that helps protect against heart disease by removing plaque from the bloodstream. The villagers had very low levels of HDL, but the mutation made it an especially effective plaque attacker.

"The concept is sort of liquid Drano for the coronary arteries," said Dr. Steven Nissen, a Cleveland Clinic cardiologist who led the study.

While some existing medicines target HDL, most conventional drug treatment works by reducing levels of LDL cholesterol, the bad kind that contributes to the formation of plaques that can clog arteries and lead to heart attacks.

The new study is part of a burgeoning area of research focusing on treatments that raise HDL levels or improve HDL's plaque-fighting abilities.

The HDL mutation was found about 25 years ago in 40 residents of the northern Italian village of Limone Sul Garda. The mutation involved a gene variation in a key protein component of HDL. That contributed to larger-than-normal HDL particles, which are believed to make HDL cholesterol especially efficient at removing plaque.

Scientists made a synthetic version, which was found to reduce plaque buildups rapidly in mice and rabbits.

The product was first tested and shown to be safe for use in humans. This latest round of experiments is the first time the substance has been used to actually treat narrowing of the arteries in people, Nissen said.

The study was funded by Esperion Therapeutics Inc. of Ann Arbor, Mich., a small biotechnology company that makes the product.

In the study, 36 patients who had had heart attacks or severe chest pain received weekly intravenous infusions of the substance for five weeks. Eleven patients received dummy treatments.

At six weeks, imaging tests showed the synthetic protein patients had a visible 4 percent reduction in plaque buildup in their coronary arteries. There was no significant change in the placebo group.

Rader called the results "surprising to even the most optimistic supporters" of using HDL to treat narrowing of the arteries.

Nissen envisions the treatment being used in combination with other therapy including LDL-lowering drugs, but said that commercial use is probably a few years off and will depend on the outcome of larger studies.

 
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