Researchers Try Fighting Heart Disease Gene by Gene

Scientists are reporting a new way to lower cholesterol. The process involves a tool called RNA interference. It uses a snippet of RNA to turn off a single gene at a time. In theory, genes responsible for producing cholesterol could be controlled to help prevent heart disease.

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Scientists are reporting a new way to lower cholesterol, and it's particularly exciting because the new approach uses a novel molecular tool that could transform standard therapies.

NRP's Joe Palca has more.

JOE PALCA reporting:

The tool is called RNA interference. It was only discovered a few years ago. Basically, it involves using a small hairpin shaped snippet of RNA to turn off a single gene at a time. So let's say you're having a problem with your cholesterol. Well, if you could shut off one the genes responsible for making cholesterol, then your cholesterol level should in theory go down.

Now scientists at Alnylam Pharmaceuticals in Cambridge, Massachusetts, have shown that's what happens, at least in monkeys. Tracy Zimmerman was the lead scientist on the project. She says they injected intravenously two differing amounts of an RNA snippet that blocks the gene that makes apolipoprotein B, a key component in cholesterol.

Ms. TRACY ZIMMERMAN (Scientist, Alnylam Pharmaceuticals): We dosed six animals at each dose level, and then we had a control group, which was just treated with saline alone.

PALCA: They then measured the levels of apolipoprotein B in these animals and as they report in the journal Nature, to their great delight, the levels of both it and serum cholesterol went down and stayed down for 11 days.

Ms. ZIMMERMAN: Well, I think that we were actually very surprised by that result. If we had evidence in mice that it was fairly long lasting, then I think that's something that we were excited to see, that this was a long lasting effect, the higher of the two doses that we tested.

PALCA: A therapy that lasts for 11 days begins to look like something that might be useful in patients. Alnylam's CEO, John Maraganore, says another piece of good news is the injections didn't cause any side effects, at least not from the single dose the animals got.

Mr. JOHN MARAGANORE (CEO, Alnylam Pharmaceuticals): We clearly have in this study, did a very careful evaluation of safety and the treatment was very well tolerated. So we believe that this is a promising approach that can have important clinical applications.

PALCA: Many scientists are thrilled by the potential of RNA interference for treating diseases. Brian Collin of Duke University in Durham is one of them. He says at first scientists didn't think the RNA snippets would last long enough to do any thing useful if they were injected into the bloodstream. He say Alnylam's results with monkeys are another example that that's changing.

Mr. BRYAN CULLEN (Scientist, Duke University): There have been a number of experiments done in rodents, in particular in a mice, that have successfully shown that RNA interference does work at the whole organism level. So in that sense it's not a surprising result. It's a predictable result, but nevertheless an important one in that it's a step on the way towards an actual drug treatment of humans.

PALCA: But there are many steps to go. Andrew Fire is at Stanford University Medical School. He's one of the people credited with discovering RNA interference in animals.

Mr. ANDREW FIRE (Scientist, Stanford University Medical School): Of course, you know, therapy in monkeys is very useful, but in people it's going to be another question. And one of the things they show here is a difference in efficacy between monkeys and mice. There could very well be a difference in efficacy between monkeys and people too.

PALCA: Still, Fire is also impressed with the new study. He says Alnylam scientists would be justified in celebrating their accomplishment. But for the time being, they's better stick to a diet that controls cholesterol.

Mr. FIRE: It's okay to have a party, but I would still have low-fat frozen yogurt at the party and not ice cream.

PALCA: The ice cream will have to wait until RNA interference is shown to control cholesterol in human patients.

Joe Palca, NPR News, Washington.

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