New kind of gene "silencing" drug works in monkeys

LONDON Wed Mar 26, 2008 2:12pm EDT

LONDON (Reuters) - A new class of drug that fine tunes the action of genes has been shown to cut cholesterol in monkeys and may fight a range of ills, including hepatitis C and perhaps cancer, scientists said on Wednesday.

The compound, from Danish biotech firm Santaris Pharma, works by blocking or "silencing" microRNAs -- tiny strands of RNA, or ribonucleic acid, that help turn genes into proteins.

The ground-breaking study is the first demonstration of microRNA silencing in primates and an early endorsement of the technique. Phase I safety trials are now planned in humans.

Unlike other drugs in the hotly pursued RNA interference field, the new designer molecule, known as Locked Nucleic Acid (LNA), can be given as a simple injection rather than having to be delivered direct to affected tissue.

"We think LNA is a one-stop shop for silencing," Santaris Chief Executive Keith McCullagh told reporters.

Scientists from Santaris and the University of Copenhagen lowered total cholesterol in African green monkeys by up to 30 percent, without ill effects, by targeting a microRNA linked to genes in the liver that are involved in cholesterol metabolism.

The results were published in the journal Nature, along with other test-tube research showing that LNA effectively blocks the production of hepatitis C virus in human liver cells.

Santaris intends to test its first LNA compounds in humans by the middle of this year but it will take at least five years before any medicine is ready for submission for approval.

While the cholesterol effect is interesting, McCullagh said the most promising opportunity actually lay in pursuing LNA as a treatment for hepatitis C, a poorly treated viral disease that can cause serious liver damage.

Further ahead, LNA could also have a role to play in other infectious diseases, as well as cancer and autoimmune disorders, since many disease-associated genes are regulated by microRNAs.

"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," said Mike Gait at the MRC Laboratory of Molecular Biology in Cambridge.

Up until now, U.S. firms such as Alnylam Pharmaceuticals Inc and Sirna Therapeutics -- which was bought by Merck & Co Inc for $1.1 billion in October 2006 -- have led the field in RNA interference.

Santaris last year signed a pact that could earn it more than $700 million with GlaxoSmithKline Plc, giving Europe's biggest drugmaker the right to develop certain products as antiviral medicines. That alliance did not include the new technology but McCullagh said Santaris could potentially extend the Glaxo deal.

For a story on Santaris Pharma's possible IPO, please click on

(Editing by Sue Thomas)

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