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May 14, 2007
 |  BioCentury  |  Product Development

Silencing a silent killer

Proprotein convertase subtilisin/kexin type 9 was linked to autosomal dominant hypercholesterolemia as early as 1999, but the specific cellular substrate of the enzyme is unknown. This challenge may make a gene silencing approach attractive, a hypothesis that will be tested under last week's deal between Isis Pharmaceuticals Inc. and Bristol-Myers Squibb Co. to discover, develop and commercialize antisense compounds targeting PCSK9 to prevent and treat cardiovascular disease.

PCSK9 is a protease that degrades specific cellular components and helps regulate the level of cholesterol in the bloodstream. People with excessive PCSK9 have high levels of LDL cholesterol, whereas those with mutations that reduce the levels of PCSK9 have lowered LDL cholesterol and reduced risk of coronary artery disease, with normal liver function.

"Our work and that...

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