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What's the Deal With the New Plaque Dissolver?

Synthetic HDL shrinks coronary artery plaques


Updated November 07, 2003

Updated November 07, 2003
In this week’s Journal of the American Medical Association, researchers report that 5 weekly intravenous injections of a new substance called ApoA-1 Milano produced significant shrinkage of plaques in patients with coronary artery disease. This finding, if confirmed in larger studies, may constitute a revolutionary breakthrough in the treatment (and possibly the prevention) of coronary artery disease.

ApoA-1 Milano is essentially a synthetic form of HDL (i.e. good cholesterol.) High levels of HDL are known to reduce the risk of coronary artery disease, apparently by “scouring” the blood vessels and removing cholesterol from vessel walls. This new substance was discovered by studying 40 people from a small town in Italy, who were known to live remarkably long and healthy lives despite having markedly reduced HDL levels. Investigators discovered that these individuals had a “mutant” form of HDL (the ApoA-1 Milano) that was not detected by routine blood testing, but that proved to be very effective in preventing cardiovascular disease. Researchers were able to synthesize the DNA mutation that produced this new HDL, and subsequently added this new DNA to a strain of laboratory bacteria – thus creating a “factory” for the production of the ApoA-1 Milano.

In the clinical study reported this week, 57 patients with coronary artery plaques were randomized to receive either the ApoA-1 Milano or placebo. The volume and thickness of their plaques were measured at the beginning of the study and again after 5 weekly injections. Those who received the active drug had significantly reduced measures of volume and thickness of their plaques; those who received placebo did not.

Since the publication of this study, the print and airwaves media have been loaded with reports from various experts describing how stunned they are by these results, and hinting as to the far-reaching implications.

DrRich Comments:

This is indeed a breakthrough study, but we all need to keep a few things in mind as we consider what this means.

First, there is no evidence that the synthetic HDL used in this study (and used to good effect by the 40 Italian villagers) is any more effective than the HDL the rest of us already have. The trick might not be in the ApoA-1 Milano itself – the trick might be in increasing HDL period, whatever form it takes.

Second, the shrinkage of the plaques observed in this study was statistically significant, but the plaques certainly didn’t disappear. The reduction in plaque volume, for instance, amounted to a few percent. The stunning breakthrough of this study was not that the plaques melted away to nothing, but that plaques could be induced to shrink AT ALL. This constitutes a proof of concept (i.e., that we can find drugs to shrink plaques) instead of a proof of treatment. More studies using, for instance, a much longer duration of treatment (months or years instead of weeks, for instance) will be necessary.

Third, under the best of circumstances this drug is several years away from being available outside of the research arena. When it is available, it is likely to be very expensive (not because drug companies are evil profit-mongers, but because the manner of producing this drug is inherently expensive). Long-term intravenous drug therapy itself is also very expensive, even if the stuff being injected is cheap.

Fourth, ApoA-1 Milano may not even be the drug that ultimately becomes the blockbuster plaque-shrinker. Several other drugs targeting HDL are under active development by a number of companies, and one of them could easily prove to be more effective or more convenient to administer than this one.

The bottom line: Plaques can be shrunk, and HDL can do it. Now that this concept has been “proven” the pharmaceutical houses have a powerful stimulus to move even more resources toward developing HDL-targeted therapy. We truly do appear to be on the threshold of a new era in the management of coronary artery disease. But it’s very early in the game.

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