Researchers Hope Man-Made 'Good' Cholesterol Will Some Day Help Lower Heart Risk
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Reviewed By Elizabeth Klodas, MD, FACC
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Jan. 16, 2008 -- Northwestern University researchers have developed a synthetic form of high-density lipoprotein (HDL), or "good" cholesterol, which they hope will lead to a clinically useful treatment for the prevention of heart attacks and strokes.
Developed using nanotechnology, which involves manipulation of matter at the molecular level, the synthetic HDL is composed of a tiny core of gold surrounded by fat molecules with an outer layer of the HDL protein ApoA-1.
Similar in size and structure to naturally occurring HDL, the synthetic compound was designed to help prevent the buildup of plaque in the arteries.
Newly reported studies from the Northwestern laboratory show that the man-made nanoparticles bind to cholesterol. This suggests that they will act as a sponge in the body to soak up the bad cholesterol that causes the formation of artery-clogging plaque, study researcher Chad Mirkin, PhD, tells WebMD.
The findings appear in the latest online issue of the Journal of the American Chemical Society.
"It not only binds, but it binds extremely well," Mirkin says. "This bodes well for its potential as a therapeutic agent. You can think of it as a cholesterol scrubber."
Synthetic HDL: Beyond the Test Tube
The next step is to test the synthetic HDL in animals and then in humans if animal studies prove promising, Mirkin says.
Mirkin directs the International Institute for Nanotechnology and Chemistry at Northwestern and is co-founder of Nanosphere Inc. in Northbrook, Ill.
Millions of people take statins to lower their LDL "bad" cholesterol. But the search for effective drug treatments to raise HDL "good" cholesterol has so far proven disappointing.
Development of one highly anticipated HDL-targeting drug, Pfizer's torcetrapib, was halted late in 2006 when phase III studies showed an excess number of deaths among people who took it in combination with a statin.
High doses of the vitamin niacin have been shown to boost HDL levels, but many people can't tolerate the side effects, which can include hot flashes.
Another synthetic HDL, known as ApoA-1 Milano, was shown to be effective for reducing plaque in patients with coronary artery disease in a 2003 study. The patients took weekly injections of the compound for five weeks.
'Treatments Years Away'
Cholesterol expert Michael Richman, MD, FACS, tells WebMD that even though the ApoA-1 Milano trial proved promising, he does not expect to see a clinically useful synthetic HDL anytime soon.
"We are a long, long way from having a targeted synthetic HDL that mimics what natural HDL does," he says.
Richman points out that it is also not clear that therapies that raise HDL will be as beneficial as those that lower LDL cholesterol have proven to be.
He points out that statins are very effective for lowering cardiovascular risk even though they don't raise HDL significantly.
Richman, who is a cardiothoracic surgeon, founded and directs the Center for Cholesterol Management in Los Angeles. He also moderates a cholesterol message board for WebMD.
"Just raising HDL to some feel-good number may not mean all that much clinically because we have no way to measure its functionality," he says.
SOURCES: Thaxton, C.S. Journal of the American Chemical Society, January 2009, online edition. Chad A. Mirkin, professor of chemistry, medicine and material science and engineering, Northwestern University. Michael Richman, MD, FACS, founder and director, Center for Cholesterol Management, Los Angeles. News release, FDA.
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