New Drug Mimics HDL “Good Cholestrol to Clear Coronary Arteries In 2 Weeks
posted 11/18/03
A synthetic form of "good cholesterol" has been shown to quickly shrink blockages clogging coronary arteries, offering for the first time the possibility of a drug that could actually rapidly reverse heart disease.

In a small, preliminary study, the laboratory-made substance, which mimics a type of cholesterol discovered in a group of surprisingly healthy villagers in rural Italy, significantly reduced in just six weeks the amount of plaque narrowing arteries of heart attack and chest pain patients, the researchers reported.

Because the approach attacks the underlying source of many heart attacks, the results could mark a milestone in the search for new ways to treat the nation's No. 1 killer, researchers said.

"For the first time, we've shown that you can reverse coronary disease with drug therapy in a matter of weeks," said Steven E. Nissen, a cardiologist at the Cleveland Clinic who coordinated the nationwide study. "We really have, for the first time, the opportunity to attack this disease at its fundamental basis. It's a paradigm shift. It's opening a new door."

Nissen and other researchers cautioned that the study only involved 47 patients, and further studies are needed to confirm the findings, fully evaluate the drug's safety and determine whether the treatment actually cuts the risk of heart attacks and strokes.
"This is the first true test of the concept that specifically targeting HDL, the good cholesterol, can impact plaque and atherosclerosis in humans," said Daniel J. Rader, director of preventive cardiology at the University of Pennsylvania, who wrote an editorial accompanying the new study in Wednesday's Journal of the American Medical Association.

Scientists have long known that there are two forms of cholesterol: One is low-density lipoprotein (LDL), which is the "bad cholesterol" because it accumulates inside artery walls, causing the vessels to narrow and setting the stage for heart attacks and strokes. The other is high-density lipoprotein (HDL), called the "good cholesterol" because it protects against heart disease, primarily by lowering LDL levels.

About 30 years ago, researchers discovered a group of about 40 people living in the small rural northern Italian town of Limone Sul Garda who had a surprisingly low rate of heart disease despite their extremely low HDL levels. Scientists determined that their HDL was slightly unusual, raising the possibility that it provided unusually powerful protection against heart disease.
Esperion Therapeutics Inc. of Ann Arbor, Mich., developed a genetically engineered form of this version of HDL, dubbed ApoA-I Milano, and showed that it reduced plaque inside the arteries of laboratory animals. The company then asked Nissen to test it in people.

In the study, Nissen and colleagues at 10 centers around the country gave weekly infusions of either the synthetic HDL or an inert placebo to 47 heart disease patients for five weeks. The plaques clogging the walls of their arteries were carefully measured before and after the treatment using an extremely precise ultrasound technique.

Compared to those who received the placebo, the patients who received the synthetic HDL experienced about a 4 percent reduction in the plaques lining their arteries, a reduction 10 times greater than anything scientists had tried previously, the researchers found.
"When the statisticians delivered the data to me, I fell off my chair," Nissen said in a telephone interview. "We've run across something that can literally clear out the plaque in just a few weeks. That's unprecedented."

Rader agreed. "I don't think anyone thought you could induce regression in six weeks -- that's the single most surprising thing about this study," Rader said.

The only other thing known to reduce plaque inside arteries is long-term use of anti-cholesterol drugs such as statins. Some research has also suggested people who strictly adhere to the Dean Ornish diet can also somewhat reverse their heart disease. But the amount of plaque reduction in those cases was just a fraction of that experienced by the patients taking synthetic HDL, and it took many years.

It remains unclear how the HDL works, but it may be especially adept at transporting LDL out of the blood and back into the liver, where it is harmlessly processed.

Rader noted that there could be nothing particularly special about this particular form of HDL. It could be that it's the only one that's been tested this way because it's a form of HDL that can be patented. Other companies are developing different ways of using HDL to fight heart disease, such as drugs that boost the body's own production of HDL.

In the meantime, Esperion plans to conduct a follow-up research that will involve thousands of patients who would be followed for a year to determine whether the treatment actually reduces the risk for heart attacks and the need for angioplasties and bypass surgery to restore blood flow to the heart muscle.

"This is a landmark study in our mind that validated the whole HDL hypothesis -- that it is something that could change the way medicine is practiced," said Roger Newton, Esperion's president and CEO.

Source: Diabetes In Control.com.

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