Researchers at DeCode Genetics, an Icelandic unit of the biotechnology firm Amgen, have identified a new genetic variant that reduces the risk of heart disease and stroke by 34%.
“This is a new biochemical pathway,” says Kari Stefansson, DeCode’s chief executive and founder. “It has not been implicated in coronary artery disease and it provides a relatively interesting drug target.”
According to a paper being published in the New England Journal of Medicine, people who had a copy of the a gene called ASGR1 that had 12 letters deleted had a 34% lower risk of heart disease. That’s “pretty substantial,” says Eric Topol, the director of the Scripps Translational Science Institute in La Jolla. The fact that the gene has a deletion means it probably doesn’t work. Topol echoed that this seems to point the way to a drug. It is far easier to block the protein a gene makes using a medicine than it is to make more of it.
Sean Harper, the head of research and development at Amgen, says the company is already readying a drug to be tested in humans. “If everything were to go perfectly, which it rarely does, we would be in a position to get a molecule into the clinic in around two years,” Harper says. Testing such a medicine in humans to find out if it prevents heart attacks will take years.
Genetic studies like those conducted by DeCode represent a new frontier for understanding why heart attacks and strokes happen, and for finding drugs based on the genes that raise people’s risk. The first such finding, from researchers at the University of Texas, Southwestern, found that patients with a gene called PCSK9 had very low cholesterol levels and a dramatically reduced risk of heart disease. That finding has led to two marketed drugs: Repatha, from Amgen, and Praluent, from Regeneron Pharmaceuticals and Sanofi.
There have now been six genetic variants that reduce heart attacks by reducing levels of proteins that move cholesterol and other fats in the blood, according to Sekar Kathiresan, director of the center for human genetic research at Massachusetts General Hospital. One is PCSK9. Another gene, called NPC1L1, is the target of another marketed drug, Zetia, from Merck.
The DeCode finding is also exciting because it doesn’t appear related only to the cholesterol number most people worry about, low-density lipoprotein or LDL, but to all cholesterol known as non-HDL cholesterol, basically cholesterol that excludes anything that isn’t high-density lipoprotein, the so-called good cholesterol that is associated with lower levels of risk. In an editorial in the New England Journal, Anne Tybjærg-Hansen, a professor at the University of Copenhagen, writes that exactly how the gene works to lower heart risk is an open question.
Another open question: Will any other drug company want to work on Amgen’s new gene? Genes themselves are not patentable. “You cannot file a patent on a biological component,” says Stefansson. “You cannot file a patent on a target.”
But Amgen didn’t buy DeCode for $415 million in 2012 just to publish in top medical journals. Harper, the Amgen research chief, says that he believes Amgen has patents around the methods of actually making a drug based on the gene.
