TIME Health Heart Disease
Doctors, and especially doctors who do research, dont like to use the words cure or eradicate. They know how dangerous that can be, since the human body is so unpredictable. But Dr. Kiran Musunuru is showing some uncharacteristic swagger about his latest success in lowering heart attack risk among some lucky mice.
Taking advantage of advances in genetic engineering, a team lead by Musunuru, who holds positions at Harvard Universitys Department of Stem Cell and Regenerative Biology and Brigham and Womens Hospital, have edited the genomes of mice and successfully protected them from heart disease. The results, published in the journal Circulation Research, hint at an entirely new way of avoiding the leading killer of Americans by possibly cutting heart attack risk by up to 90%. What has me excited as a cardiologist is that my goal is eradicating disease, says Musunuru. There is no bolder way I can put it. I want to eradicate the disease and this offers one potential way to do it.
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He admits that it may be 10 years or more before the technique is ready for testing in people, but these first results are enough to justify the research that could make that happen. This approach in general will be a game changer, says Dr. Deepak Srivastava, director of cardiovascular disease and stem cell biology and regenerative medicine at the Gladstone Institutes, who was not affiliated with the study.
Heres how they did it. In 2003, genetic information was gleaned from a French family that carried a genetic mutation giving them low LDL cholesterol, the kind that, when its high, can lead to heart disease. Using a new genetic engineering technique that allows scientists to splice more efficiently into specific locations on a genome, Musunuru was able to essentially bestow the genetic advantage from the French family onto his mice, slowing down production of a protein that normally keeps LDL circulating in the blood. With less of the protein around, less LDL remains in the blood; those with the PCSK9 mutation showed as much as an 88% lower risk of heart disease compared to people without the genetic change.
The genetic monkeying was accomplished with the help of a virus, which has a remarkable ability to get into cells. The virus was injected, along with the DNA-disrupting machinery, into the liver of the mice. Within days, more than half of the liver cells had been genetically edited and the mice showed 35% to 40% less cholesterol in the blood.
So far, says Musunuru, there have been no negative effects of the genetic disruption. But he says more research needs to be done to make sure that introducing the changes wont come with unforeseen consequences. When we go in there we want to make sure we are not introducing new spelling errors in the genome, says Srivastava, who is also using the technique for stem-cell based therapies to treat heart disease. Says Musunuru, I think I can confidently say that with this tool, this technology will work on live, breathing human beings, but we need to figure out the safety; thats the barrier to overcome before we can test these therapies.
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Drug companies are also working on drug-based ways to interfere with PCSK9, and lower LDL levels, but those therapies are antibodies that bind to the protein that the gene makes and need to be injected, at a doctors office, regularly. The genome editing strategy would be a one-stop therapy that could permanently protect against excessively high cholesterol levels.
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