WEDNESDAY, Jan. 10 (HealthDay News) -- A new drug that helps people with a severe, inherited form of high cholesterol looks promising, a study found.

But even the researchers, who report their findings in the Jan. 11 issue of the New England Journal of Medicine, caution that the compound has its downsides and the study was small.

Dr. Daniel J. Rader, director of preventive cardiology at the University of Pennsylvania School of Medicine, and his colleagues gave the drug to six people with a condition called homozygous familial hypercholesterolemia (FH), in which a gene mutation makes cholesterol levels abnormally and dangerously high.

Those with FH typically develop cholesterol problems early and may get heart disease before they reach the age of 20; they generally don't live past the age of 30.

"It's a very rare condition, one in a million," Rader said. That means about 300 people in the United States have it, he said. But the hope is that the new compound, once perfected and studied more extensively, might also help people who don't have FH but who do have cholesterol problems and don't tolerate statins well.

About 40 million people in the United States should be on cholesterol-lowering statins, Rader said, but up to 5 percent don't tolerate statins.

In the new study, Rader's team gave the drug to six men and women, aged 18 to 40, who all had FH. The compound, originally called BMS-201038 but now known as AEGR-733, was given in four different, escalating doses, each dose for four weeks.

The highest dose was 1 milligram per kilogram of body weight. "At the top dose, which everyone tolerated, there was a 51 percent reduction in LDL," Rader said. LDL is "bad" cholesterol.

"For these patients, 51 percent is huge," he said. "On standard drugs, they are likely to get no reduction, or maybe 5 percent."

While the study did not look at whether the 51 percent reduction reduced heart disease risk, it is likely that it does, Rader said. "Someone whose LDL is 300 [milligrams per deciliter of blood] is at much lower risk than someone at 600," he noted.

Typically, patients with FH have total cholesterol of 600 to 1,000. Below 200 is ideal. The six patients studied had total cholesterol levels of 684 to 1,212; their LDL at the beginning was 480 to 789. (Ideal LDL depends on your level of heart-disease risk; for very high-risk people, under 70 is often suggested.) On the highest dose, LDL levels fell to between 201 and 403.

"The new drug actually targets the ability of the liver to make LDL, to make and assemble it and put it into the bloodstream," Rader said. "The liver still makes some, but it is markedly reduced."

The researchers did find some downsides to the drug, including accumulation of fat in the liver. They noted in the report that this side effect "could present a serious barrier to the clinical use of this class of agents."

Dr. Steven E. Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic, called the study results "very impressive." Coming up with a new class of drugs for people affected by this condition, he said, is very important. It also suggests another approach for lowering cholesterol besides statins. "Not everyone can tolerate a statin drug," he said.

But, he noted the accumulation of fat in the liver, and potential damage from that. The study was also small, only six people, "so we have no real knowledge of safety" of the drug, Nissen said.

Dr. Sergio Fazio, co-director of the Atherosclerosis Research Unit in the division of cardiovascular medicine at Vanderbilt University, said he, too, was concerned about the fat build-up in the liver.

"This drug does what it promises to do -- block droplets of fat from moving out of the liver and into the bloodstream," he said. "But fat builds up in the liver and causes loss of liver cells, and it's not clear that this is a good trade-off."

Perhaps the next step should be to find a way to modify the compound, or to investigate the use of a second drug that could prevent or reduce that fat build-up in the liver, Fazio said.

Rader said he hopes to get the drug "fast-tracked" by the U.S. Food and Drug Administration and to have it on the market by 2010, if all goes well in future studies. The university has licensed the drug to Aegerion Pharmaceuticals Inc. for further development. Rader has an equity interest in Aegerion Pharmaceuticals.

More information

To learn more about lowering cholesterol, visit the U.S. National Heart, Lung, and Blood Institute.