In the collaboration, researchers from the company and the University’s Southwestern Medical Center will evaluate the use of RNAi therapeutics directed to a disease target called proprotein convertase subtilisn/kexin type 9, or PCSK9.
PCSK9 is an important gene involved in the metabolism of LDL-cholesterol, or so-called bad cholesterol. The normal role of the PCSK9 protein is to break down the LDL receptor (LDL-R); when there is less PCSK9 protein, there is more LDL-R on the cell surface.
Research at UT Southwestern Medical Center has shown that reductions in the levels of PCSK9 protein can lead to significant reductions of LDL in the blood, and in fact mice lacking PCSK9 have significantly decreased cholesterol with no other adverse phenotype.
“Although PCSK9 is validated based on human genetics, it has been a difficult protein to target using traditional drug discovery approaches. Therefore, we believe it is an ideal target for a systemic RNAi approach in light of our recent progress with systemic delivery of RNAi therapeutics,” Dr Victor Kotelianski, vice president of research for Alnylam Pharmaceuticals.