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Friday, June 15, 2007 3:12:06 AM
Little hopes
Jun 14th 2007
From The Economist print edition
New classes of drugs that exploit the new RNAs are in development
DRUGS based on RNA interference (see article http://www.economist.com/science/displaystory.cfm?story_id=9333471 ) are still being tested, but they are moving within striking distance of the market. Opko Corporation, based in Miami, is planning its final round of clinical trials for an RNAi drug later this year. The drug is designed to halt a disease called wet age-related macular degeneration, which is one of the most common forms of blindness in elderly people. It works by stopping the manufacture of a protein called VEGF, which is over-produced in the disease.
In the past two years investment has poured into two larger RNAi specialists, which both claim more intellectual property than Opko. In September 2005 Novartis, a big drug company, promised one of these ambitious young hopefuls, Alnylam Pharmaceuticals, $700m if it creates real medicines from its science. In April 2006 GlaxoSmithKline, another of the pharmaceutical industry's ruling elite, dangled the same figure in front of Alnylam's main rival, Sirna Therapeutics. Then, in December, Merck gobbled Sirna for $1.1 billion—more than twice Sirna's stockmarket value. Although the company has finished only one clinical trial, Ted Tenthoff, of Piper Jaffray, an investment bank, thinks that price may prove cheap.
There is, however, an obstacle to turning RNAi into the next broad category of drug. Opko's eye treatment can be popped straight into the eyeball with a needle. Inside a cell, or an enclosed space like an eyeball, RNAi works like a charm. Often, though, a drug must hitch a ride in circulating blood to reach the diseased part of the body it is aimed at. RNA is not tough stuff. Enzymes in the blood destroy it quickly. Even those in a breath that is carelessly exhaled over a test tube can ruin an RNA experiment. Most RNAi drugs will probably have to be encased in lipid bubbles to protect them. At the moment RNAi companies are designing bubbles that unload their contents when they find the right sort of diseased cell.
If that problem can be solved, a subsequent wave of medicines might come from microRNAs. When a cell stops making a crucial microRNA, the proteins it would have controlled are produced in abnormally large amounts. Conversely, if the cell makes too much of the microRNA, too few of those proteins will be produced. These sorts of changes have been linked to Tourette's syndrome and to many cancers. Alnylam and Merck hope that restoring the microRNA's levels by adding it to the cell (or, by contrast, adding something called an antagomir, which sticks to microRNAs and prevents them working) will eventually remove the disease.
http://www.economist.com/science/displaystory.cfm?story_id=9333482
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