Cholesterol Vaccine

Let me say that again. Cholesterol Vaccine. Does't sound logical does it? According to an article in the Feb. 2002 issue of Scientific American called Down With The Bad, Up with the Good (by Thomas Maeder), that is exactly what a biotech firm called Avant Immunotherapeutics is developing. As the title suggests, the vaccine doesn't prevent cholesterol, but helps increase the levels of high-density lipoprotein (HDL) or the good cholesterol, while lowering the amount of low-density lipoprotein (LDL) or bad cholesterol. Using a vaccine to accomplish this task, instead of direct chemical intervention, is a novel idea, and promises to be more effective with fewer side-effects.

Previous studies have shown that high levels of HDL and low levels of LDL correspond with a low incidence of cardiovascular disease. A certain amount of cholesterol of both types is needed for proper functioning of hormones, cell membranes, and other biological functions. But too much LDL can lead to the build-up of plaque on the walls of vital arteries, constricting blood flow and leading to heart disease.

As part of the process, something called cholesteryl ester transfer protein (CETP) transports cholesterol from the arteries to the liver, and helps convert HDL into LDL. Reasoning that if you could block the action of CETP the amount of LDL in the bloodstream would decrease, while the accumulated HDL would increase, several drug manufacturers began to look for a substance to limit the activity of CETP. Avant took a different approach toward the same goal. Their plan was to trigger a limited immune response to the CETP molecule. Another researcher, Alan R. Tall of Columbia University had already identified a likely target, a string of 16 amino acids in the CETP molecule that was vital to its functioning, yet was distinct to CETP - the same sequence did not appear in any other naturally occurring proteins in the body.

The next step was to synthesize a stable yet safe molecular structure that would attach to the CETP and make it appear like a threat to the immune system. To do this they created a sequence of amino acids complementary to the sequence identified by Tall, so they would attach to the CETP molecule. Then they linked that with a sequence of 14 amino acids from the tetanus toxin. Since most Americans have had tetanus shots, their immune systems should already be primed to destroy those sequences, taking along the CETP as they do.

When tested in rabbits, the vaccine lowered LDL by 24 percent, raised HDL by 42 percent. These encouraging results lead to FDA approval for clinical studies. Human safety testing has been completed, and the company is moving into phase II tests to determine the optimal dosage. Other companies are experimenting with similar techniques to treat other conditions, such as Alzheimer's, cancer, and even contraception.

One of the great benefits of these immunological strategies is that a single dose will remain effective for six months or more, in contrast to daily treatment by drug therapy. Also, in taking advantage of the natural defense mechanisms, the treatment is highly targeted, so there are less likely to be side-effects..




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