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How To Lower Cholesterol: New Drug 'Cuts Cholesterol Levels Up To Almost 60%'

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A radical new approach to lowering cholesterol has been demonstrated using an advanced gene-silencing drug.

One dose of the experimental drug cut levels of the "bad" form of cholesterol in healthy volunteers by up to 57%.

Scientists believe the drug, known as ALN-PCS, could provide an alternative treatment for patients with high cholesterol who do not respond well to conventional statins.

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The drug employs a concept known as RNA interference (RNAi). Small pieces of the genetic molecule RNA are used to shut off a particular gene by interfering with its coded instructions.

In this case, the gene in question produces a protein called PCSK9 that reduces the body's ability to clear away harmful cholesterol naturally.

"Bad" cholesterol, low-density lipoprotein (LDL), plays a major role in the build up of scale-like deposits on the walls of arteries that impede blood flow and increase the risk of heart attacks and strokes.

See Also: Foods To Lower Cholesterol And Prevent Heart Disease

Researchers conducting a pilot trial recruited 32 healthy volunteers aged 18 to 65 who all had mildly to moderately raised levels of LDL.

They were randomly assigned either to receive injections of the new drug, or a non-active placebo in the form of a salt water solution.

Infusion of ALN-PCS led to a rapid dose-dependent drop in blood-levels of PCSK9. In volunteers given the highest dose, LDL cholesterol levels also fell by an average of 40% and as much as 57% compared with the placebo group.

The findings are published in the latest edition of The Lancet medical journal.

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Lead investigator Dr Kevin Fitzgerald, from the US company Alnylam Pharmaceuticals, which developed the drug, said: "If successfully developed, this class of drugs could be an alternative for the one in five people who are resistant to statins, or be combined with statins to produce even greater effects for the many others for whom the current first-line treatment does not lower cholesterol enough.

"This marks the first time that the effect of an RNAi drug candidate has been demonstrated on a clinically validated endpoint, performing as well as statins that provide about 36% to 53% drops in LDL cholesterol.

"The next step will be larger multi-dose studies without the use of pre-medication to address long-term safety and tolerability of ALN-PCS in various patient populations, including those on statins and those who are statin intolerant."

Commenting on the study, Professor John Burnett and Dr Amanda Hooper from the University of Western Australia, wrote in The Lancet: "PCSK9 inhibition is shaping up to be an effective means of lowering LDL cholesterol in patients with severe or refractory hypercholesterolaemia (excessively high cholesterol) who are not able to tolerate statins or have not reached target concentrations of LDL cholesterol.

"Since statins up-regulate PCSK9, potentially limiting their effectiveness, combination treatment with the addition of a PCSK9 inhibitor could enhance the LDL-lowering effect of statins alone."

Professor Peter Weissberg, medical director at the British Heart Foundation, said: "People with extremely high cholesterol are at increased risk of a heart attack and this approach could offer new hope for those who are resistant to statins.

"These initial results add to growing evidence that blocking the action of a certain protein can dramatically lower 'bad' LDL cholesterol. More research is now needed to confirm this approach is both safe and effective at preventing heart attacks in the long term before it becomes widely available."

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