Amgen Researchers Discover Gene that Cuts Heart Attack Risk

May 19, 2016
By Mark Terry, BioSpace.com Breaking News Staff

deCODE genetics, based in Reykjavik, Iceland, a subsidiary of Amgen , reported the identification of a gene that seems to be responsible for a 35 percent reduction in heart attack and coronary artery disease risk.

The study is being published today in the online edition of the New England Journal of Medicine. An analysis of genetic data across Iceland identified a deletion in the ASGR1 gene on chromosome 17 that was 12 letters long and is related to non-HDL cholesterol. It was then duplicated in more than 300,000 people in the Netherlands, Denmark, Germany, New Zealand, the United Kingdom and the U.S.

“We know we have put our finger on something fundamental when we find a single variant that confers on carriers an average one year of extra lifespan,” said Kari Stefansson, founder and chief executive officer of deCODE, in a statement. “Our unrivalled population resources and knowledge of genetics in Iceland put us in a privileged position to systematically discover such low-frequency variants. As our model expands to different corners of the globe, we expect to accelerate our discovery and validation efforts to many populations and all continental ancestries. This is the promise of the big genetics paradigm that we pioneered and that is now delivering to the benefit of patients around the world.”

One of the many interesting things about this finding is that the deletion doesn’t seem related to low-density lipoprotein, or LDL, which is the so-called “bad cholesterol.” It relates to non-HDL cholesterol, which is everything that isn’t high-density lipoprotein. Not only did the deletion give individuals a significant reduction in non-HDL levels, it seemed to give them greater protection against coronary artery disease and heart attacks.

Because it’s a relatively straightforward deletion, it would also be amenable to drugs that block the ASGR1 protein, which Amgen is already working on.

What is not quite as clear is why this particular mutation seems to provide such broad cardiac health protection. In a New England Journal of Medicine editorial written by Anne Tybjaerg-Hansen, with the University of Copenhagen, says, “Nioi and colleagues identify ASGR1 as a link between the sialylation pathway, plasma levels of non-HDL cholesterol, and coronary artery disease. Thus, this association may suggest a new path to the development of future therapies for the prevention of coronary artery disease. However, mechanisms by which loss-of-function mutations in ASGR1 cause large reductions in cardiovascular risk remain to be determined.”

“If everything were to go perfectly,” said Sean Harper, head of research and development at Amgen, to Forbes, “which it rarely does, we would be in a position to get a molecule into the clinic in around two years.”

Since genes can’t be patented, other drug companies could also try to develop drugs inhibiting the ASGR1 protein. Harper suggested, however, that Amgen may have patents related to technology to make a drug based on the gene. Nonetheless, the discovery is provocative enough that many companies will be taking a hard look at the subject.

It was this type of variant that led to the development of PCSK9 inhibitors. Currently, the two PCSK9 inhibitors on the market are Sanofi and Regeneron ’s Praluent, and Amgen (AMGN)’s Repatha.