New IV drug mimics HDL - Liquid Drano for plaque in blood vessels
Nov. 4 — Intravenous doses of a synthetic component of “good” cholesterol reduced artery disease in just six weeks in a small study with startlingly big implications for treating the nation’s No. 1 killer. “The concept is sort of liquid Drano for the coronary arteries,” said Dr. Steven Nissen, a Cleveland Clinic cardiologist who led the study.
‘This is clearly on the level of a breakthrough that will have far-reaching implications.’ — DR. BRYAN BREWER
Chief of molecular diseases at the National Heart, Lung and Blood Institute LARGER AND LONGER studies need to be done 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 treatment used a laboratory-produced version of an unusually effective form of HDL, the good cholesterol that helps protect against heart disease by removing plaque, or fatty buildups, from the bloodstream.
“This is clearly on the level of a breakthrough that will have far-reaching implications,” 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 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.
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.
RAISING HDL LEVELS
Nissen’s study is part of a burgeoning area of research that focuses on treatments that raise HDL levels or improve HDL’s plaque-fighting abilities.
His findings stem from an unusual discovery about 25 years ago in the northern Italian village of Limone Sul Gardia. Italian researchers found that 40 residents there had very low HDL levels, yet paradoxically had low rates of coronary artery disease.
Lab tests revealed a likely explanation: All had a gene variation in a key protein component of HDL. The variation contributed to larger-than-normal HDL particles, which is believed to make HDL cholesterol especially efficient at removing plaque.
Scientists made a synthetic form of the protein, 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.
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 patients receiving the synthetic protein 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 said he envisions the treatment being used in combination with other therapy including LDL-lowering drugs, but that commercial use is probably a few years off and will depend on the outcome of larger studies.
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This is really interesting--if it works. I know the focus is on post-cardio patients. However, imagine what this would do for neural arteries as we age!
Chelation therapy started with alot of hype. I know that clinical trials are still being run--but honestly, you don't hear much about it now.
And we'll collect the moments one by one. I guess that's how the future's done. Feist, "Mushaboom", 2005
Testosterone users may already be getting the same benefits, but via a different mechanism with the same end result: increased cholesterol transport away from arteries. Severed Ties posted an abstract showing testosterone increases reverse cholesterol transport, the same action responsible for the antiplaque effect of the larger HDL particles in Trevdog's post:
About halfway down the page I tried to translate the somewhat sophisticated language of the abstract into simpler terms:
Did you want a simplified interpretation of the article, Severed Ties? I don't know enough to say this process they are describing would tip the scales away from plaque formation (atherogenesis) even though HDL levels are lower. I doubt anyone knows that yet. But basically the process they are describing works like this:
Macrophages are immune cells that adhere to the walls of blood vessels. They have the abillity to soak up cholesterol from the blood and form so called foam cells, which contribute to the formation of atherosclerotic plaque on the vessel walls. HDL particles on the other hand transport cholesterol from cells in general to the liver. When HDLs attach to extrahepatic (i.e., not liver) cells that have too much cholesterol, they absorb some of the excess cholesterol and carry it to the liver where it is excreted in the bile. The presence of SR-BI on the surface of cells is what allows HDL particles to bind to the cells, remove their cholesterol, and carry it to the liver for disposal.
When the cells in question are macrophages attached to the vessel walls, HDL attaches to the macrophages and removes their cholesterol so they can't become foam cells and contribute to plaque formation. Obviously if testosterone increases the number of SR-BI receptors on macrophages, it makes it easier for HDL particles to attach and carry away the cholesterol in the macrophages.