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New Cholesterol Drugs Mimic Healthy Genomes

MIT's Technology Review offers a rundown this week of several pharma projects using the genes of healthy people to inspire new cholesterol-lowering drugs.

Four companies, Pfizer, Amgen, and Alnylam, and a firm called Regeneron, are all developing drugs targeting the gene PCSK9, Tech Review's Susan Young writes.

Variations in PCSK9 have been associated with reduced low-density lipoprotein, LDL, or "bad" cholesterol. Young cites a 2006 New England Journal of Medicine study, which found that subjects with nonsense mutations in PCSK9 had reduced LDL cholesterol levels and a lower risk of coronary heart disease.

Specifically, the study found that black subjects with mutated PCSK9 had a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD and white subjects had a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD.

According to Young, researchers from Regeneron — which leads the pack in its progression toward late-stage clinical trials — are developing an "antibody-based therapeutic, which binds to the PCSK9 protein and blocks it from interacting with the LDL receptor." Presumably, this will allow the receptor to remove more LDL from the blood.

Alnylam is taking a gene-silencing approach toward the same effect, according to Young, while both Amgen and Pfizer have also reported promising results from mid-stage clinical trials of their PCSK9-targeting drugs.

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