One-off injection cuts cholesterol

A single injection of a new drug could cut cholesterol levels by two-thirds, significantly reducing 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 - 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 being developed using "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 this week in the online version of the journal Nature, showed that RNA interference caused a 75 per cent reduction in harmful cholesterol.

The effect was seen within 24 hours of treatment and lasted for at least 11 days after a single injection, said John Maraganore, the chief executive of Alnylam, a biotechnology company in Cambridge, Massachusetts.

"It represents a major step forward in the development of therapeutics based on RNA interference."

Existing anti-cholesterol drugs called statins can reduce harmful cholesterol by between 30 and 40 per cent but they must be taken daily.

An injectable drug based on RNA interference was potentially more powerful and longer lasting.

The study involved injecting tiny fatty droplets loaded with RNA molecules into the bloodstream of the monkeys. These droplets released their contents in the liver.

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.

It was the first time scientists had shown it was possible to reduce cholesterol levels in primates with an injectable version of a drug based on RNA interference. Previous studies were on laboratory mice.

The importance of the findings was that it showed it was potentially possible to treat patients by injecting drugs into the bloodstream rather than 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.

- INDEPENDENT