Cells' disease machinery silenced

The initial hope is for a treatment for the liver disease Hepatitis C

Scientists say they have taken a major step towards a new generation of drugs for many conditions, including cancer.

Writing in Nature, a Danish team said they had "silenced" key genetic material in cells called RNA, thought to play an important role in disease.

Working on monkeys, they cut the animals' cholesterol levels by silencing strands of micro-RNA in liver cells controlling its metabolism.

Previous tests had only been carried out in a test-tube, or on rodents.

The study holds out hope for the treatment of liver diseases.

The team from the Copenhagen-based drug firm Santaris Pharma are aiming to use their findings to develop a treatment for Hepatitis C rather than high cholesterol, for which there are already a number of effective treatments.

But they say the technique could ultimately be employed to treat a range of conditions, including certain types of cancer, cardiac diseases and metabolic problems like diabetes.

Taking charge

The treatment is based on the idea of silencing certain types of RNA, which scientists have increasingly come to understand as the main regulator of what goes on in a cell.

We are going to have to take it slowly, but it is nonetheless a possibility that we could have something on the market within five years Dr Keith McCullagh Santaris Pharma

Types of RNA have been identified which have been associated with disease.

There is evidence to suggest, for example, that levels of one form of RNA are extremely elevated in lymphomas, and that they are not just a symptom but a driver of the disease.

Silencing them could therefore prove an effective treatment, if not a cure.

The experiment featured in Nature shows for the first time that it is possible to employ this silencing technique in non-human primates.

African green monkeys were injected with a drug aimed at silencing microRNA-122, which is known to have a role in the production of cholesterol.

After three doses over five days, their cholesterol levels were lowered by 30% - an effect which lasted for three weeks.

"What's more, there appeared to be no associated signs of toxicity to the liver or kidneys," said Joacim Elmen, part of the Santaris Pharma team.

Side-effects unknown

However, the side-effects of silencing RNA remain unknown.

There are great prospects for future drug development both for liver diseases and other disease types Dr Mike Gait MRC Laboratory of Molecular Biology

While the team hope to use their findings to develop a treatment for Hepatitis C, which is also regulated by microRNA-122, it is unclear what the implications of permanently lowering both "good" and "bad" cholesterol at the same time would be.

This would in any event be one of the known side-effects. There may be others which are not yet apparent, including the risk of developing liver cancer, admits Dr Keith McCullagh, the head of Santaris Pharma.

"We are going to have to take it slowly, but it is nonetheless a possibility that we could have something on the market within five years," he said.

Dr Mike Gait, of the MRC Laboratory of Molecular Biology in Cambridge said: "This exciting paper is the first to show activity in monkeys of an important new class of designed molecule that can interfere with an essential RNA that controls specific genes in the liver.

"There are great prospects for future drug development both for liver diseases and other disease types, and Europe has the potential to match the USA in this area."