RNA therapy trial success

The first clinical trial based on a promising new technology called RNAi (RNA interference) has shown that it could soon be used to treat an eye disorder. The trial was designed to test the safety of the technique for treating a disease called wet age-related macular degeneration (AMD). This condition, which is the leading cause of adult blindness in the developed world, is caused by the abnormal growth of blood vessels behind the retina. Preliminary results from the trial, reported by US biotech firm Acuity Pharmaceuticals at the recent American Society of Gene Therapy (ASGT) meeting, show that the new therapy has reduced blood vessel growth and slightly improved patients' vision.

The symptoms of AMD appear when the abnormal blood vessels leak blood and fluid, damaging light-sensitive cells in the retina. The new trial involved injecting an RNA treatment called Bevasiranib directly into the patients' eyeballs, to try and halt the disease. RNAi is a naturally-occurring cell process, which is now being exploited as a way of selectively shutting down gene activity. It involves injecting cells with short, specific pieces of RNA, which then trigger the breakdown of a particular mRNA (messenger RNA) molecule - the intermediate stage between a gene and the protein it codes for. In this way, scientists can selectively shut down production of any protein made by the cell, without affecting any others.

In the AMD trial, the researchers hoped that the injected RNA would switch off production of a protein called vascular endothelial growth factor (VEGF), which in turn would stop growth of the blood vessels. When the trial was launched, Samuel Reich of Acuity, said that in contrast to previous treatments for AMD aiming to block the action of VEGF, which 'act like a mop in a leaky basement', RNAi 'turns off the leak at the faucet'. Now, preliminary results from the 129 participants show that the approach appears to work, with the effects lasting several months - even at the lowest doses. 'It's a very encouraging result', Acuity president Dale Pfost told Nature News.
The researchers say that Bevasiranib could be used in combination with existing drugs that stop blood vessel growth by blocking VEGF, to provide a long-term treatment for AMD. According to Mark Kay, president of the ASGT, the trial represents a milestone for RNA therapies. 'I'm cautiously optimistic that RNAi will be useful in the clinic and that this will be established relatively soon', he said.