Scientists 'silence gene' to slash cholesterol levels
Monday, 27 March 2006
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A single injection of a new type of drug could cut cholesterol levels by two thirds and significantly reduce the risk of heart disease and blocked arteries, a study has found.
Scientists have successfully interfered with the gene involved in producing high levels of harmful cholesterol in the bloodstream using a treatment that promises to revolutionise medicine.
Using synthetic molecules of RNA - a close relative of DNA, the molecule of inheritance - scientists have silenced the gene for apolipoprotein B (apoB), which plays a critical role in the metabolism of cholesterol.
The treatment is one of many that are being developed using the phenomenon of RNA interference which promises to create new ways of tackling a range of illnesses from cancer and genetic disorders to viral infections.
The researchers used small molecules of RNA that were targeted against the apoB gene of monkeys. The study, published today in the online version of Nature, showed that RNA interference caused a 75 per cent reduction in the harmful low-density version of cholesterol.
The effect was seen within 24 hours of the monkeys being treated and it lasted for at least 11 days after a single injection, said John Maraganore, the chief executive of Alnylam, a biotechnology company in Cambridge, Massachusetts.
"We have shown that an injection of our drug into the bloodstream of primates can result in a profound and durable silencing of a disease-causing gene," Dr Maraganore said. "It represents a major step forward in the development of therapeutics based on RNA interference," he said.
Existing anti-cholesterol drugs called statins can reduce the harmful version of cholesterol by between 30 and 40 per cent but they have to be taken daily. An injectable drug based on RNA interference is potentially more powerful and longer lasting, Dr Maraganore said.
"One of the things that was remarkable was the durability of the effect after a single injection of this drug," he said.
The study involved injecting tiny fatty droplets loaded with RNA molecules into the bloodstream of the monkeys. These droplets were carried to the liver where they released their contents.
Cells in the liver took up the small molecules of RNA which then began to interfere with or "silence" the gene responsible for making the apoB protein involved in the production of cholesterol.
The result was a 75 per cent reduction in levels of the apoB protein, a more than 60 per cent reduction in cholesterol and a more than 80 per cent reduction in the harmful low-density lipoprotein version of cholesterol.
Dr Maraganore said there were few signs of side effects except at very high doses and these were relatively minor and reversible.
Alnylam hopes to be able to move to clinical trials with human volunteers within the next two years, he said.
This is the first time that scientists have demonstrated that it is possible to reduce cholesterol levels in primates with an injectable version of a drug based on RNA interference. Previous studies showed that it worked on laboratory mice.
The importance of the findings is it shows that it is potentially possible to treat patients using the "systemic" approach of injecting the drugs into the bloodstream rather than directly into certain target organs.
Alnylam are also developing ways of administering RNA interference drugs using inhalation sprays to treat respiratory illnesses.
Acuity of Philadelphia and Sirna of Boulder, Colorado, are developing RNA interference to treat macular degeneration of the eye.
