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Alnylam Announces Collaboration with UT Southwestern Medical Center
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Alnylam Pharmaceuticals, Inc. has announced that it has entered into a collaboration with University of Texas Southwestern Medical Center at Dallas to evaluate approaches for reducing LDL-cholesterol levels using RNAi therapeutics directed to a disease target called proprotein convertase subtilisn/kexin type 9, or PCSK9.
"It is very exciting for us to be partnering with UT Southwestern Medical Center, one of the world's leading academic centers in the area of cholesterol metabolism," said Victor Kotelianski, M.D., Ph.D., Vice President of Research for Alnylam Pharmaceuticals.
"PCSK9 is a compelling target for potential breakthrough treatments of hypercholesterolemia and complications of acute coronary syndromes."
"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."
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.
The collaboration will utilize systemic RNAi technologies developed by Alnylam such as those described in its recent Nature paper in primates (Nature 441: 111-114, 2006) where systemic RNAi targeting apolipoprotein B (apoB), another protein involved in cholesterol metabolism, resulted in dramatically reduced levels of apoB mRNA and protein and resulted in a greater than 65 percent lowering of cholesterol and a greater than 85 percent lowering of LDL.
"We believe PCSK9 is an excellent target for the potential development of RNAi therapeutics based on data from human genetic studies, and this approach holds significant promise for controlling LDL-cholesterol levels in humans," said Jay Horton, M.D., Associate Professor of Internal Medicine and Molecular Genetics, UT Southwestern Medical Center.
"I have been impressed with Alnylam's ability to silence disease-causing genes with RNAi as evidenced in their 2006 Nature paper and look forward to working with them to evaluate an RNAi approach targeting PCSK9."
Human mutations in PCSK9 that increase PCSK9 activity are linked with an autosomal dominant form of hypercholesterolemia.
In turn, recent research published in the New England Journal of Medicine (N. Engl. J. Med. 354, 1264-1272, 2006) has demonstrated that human polymorphisms that lower PCSK9 function are associated with an 88 percent risk reduction in coronary heart disease.
