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Designer RNA Fights High Cholesterol

By R&D Editors | August 12, 2008

Small, specially designed bits of ribonucleic acid (RNA) can interfere with cholesterol metabolism, reducing harmful cholesterol by two-thirds in pre-clinical tests, according to a new study by researchers at UT Southwestern Medical Center in collaboration with Alnylam Pharmaceuticals and the Massachusetts Institute of Technology.

In a study that appears online and in an upcoming issue of the Proceedings of the National Academy of Sciences, researchers found that a single dose of a small interfering RNA (siRNA), a chemical cousin of DNA, lowered cholesterol levels up to 60 percent in rodents, with the effects lasting for weeks. This result indicated that the RNA interference, or RNAi, mechanism could provide a new tactic for treating high cholesterol. Similar treatments in four nonhuman primates, conducted off-site by a certified contract research organization, produced an average 56 percent drop in low-density lipoprotein cholesterol levels in the animals’ blood.

The siRNA works by jamming the production of PCSK9 (proprotein convertase subtilisin/kexin type 9), a protein that normally raises the level of LDL cholesterol, the “bad” cholesterol that tends to create fatty deposits inside blood vessels.

Studies by other UT Southwestern researchers have found that people with mutations in the PCSK9 gene, which prevented them from making normal levels of the PCSK9 protein, had LDL cholesterol levels 28 percent lower than individuals without the mutation and were protected from developing coronary heart disease.

Release date: August 11, 2008
Source: UT Southwestern Medical Center 

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