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RNA therapy tackles eye disease

June 6, 2006 By Jacqueline Ruttimann This article courtesy of Nature News.

Blocking genes stops blood vessels covering retina.

The commonest cause of blindness in the elderly has been treated with small pieces of genetic material that block genes. The result comes from the first clinical trial to assess the effectiveness of a therapy known as RNA interference (RNAi).

The trial tested a drug called Bevasiranib on patients suffering from age-related macular degeneration (AMD), which erodes vision as blood vessels grow on the retina at the back of the eyes. The currently incurable condition affects about 1.65 million Americans.

Bevasiranib was developed by Acuity Pharmaceuticals of Philadelphia. The company estimates that 11 million people worldwide will have AMD by 2013.

The trial on 129 patients found that Bevasiranib reduced blood-vessel growth in the eyes and improved vision slightly. At the lowest doses, these effects lasted for several months; at higher doses the positive responses are still present, says Dale Pfost, Acuity's president. No adverse side effects were seen other than the anticipated swelling and inflammation at the site where the drug was injected into the eye.

"It's a very encouraging result," says Pfost, who announced the preliminary findings at the meeting of the American Society of Gene Therapy in Baltimore on 1 June.

Stunted growth

Bevasiranib turns off the gene for a molecule called vascular endothelial growth factor (VEGF), which stimulates blood-vessel growth across the retina of AMD patients. The drug uses short sections of RNA, the molecular cousin of DNA, which often ferries genetic information around cells.

Short, interfering RNA (siRNA) strands stick to cellular RNA molecules that trigger the growth factor's production. The siRNA carries a chemical unit that marks its quarry for destruction by the cell's proteins. Less RNA means less growth factor, slowing the proliferation of blood vessels.

The siRNA molecules do not appear to interact with DNA, easing concerns that the drug will alter patients' genetic make-up. This is seen as a threat in other types of gene therapy, and has been suggested as the cause of leukaemia in three patients in a recent French gene-therapy trial (see ' Gene therapy put on hold as third child develops cancer').


Pfost says that Bevasiranib could be used in combination with other drugs, such as the anticancer drug Avastin, that block the effects of VEGF. Ophthalmologists who have given their AMD patients Avastin have seen some encouraging results, but the effects only seem to last a few weeks. Bevasiranib could beat the disease in the longer term, says Pfost.

The successful trial is a milestone in the development of RNA therapies, says Mark Kay, an RNAi researcher at Stanford University, California, and president of the American Society of Gene Therapy. "I'm cautiously optimistic that RNAi will be useful in the clinic and that this will be established relatively soon," he says.

Formal results of the Phase 2 trial of Bevasiranib will be revealed in September. Phase 3 trials of are expected to start at the end of 2007, with final results anticipated in 2009.

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