Utah scientists link mutation to blindness

Utah scientists have discovered a common genetic mutation that vastly increases a person's risk of macular degeneration, the most common cause of blindness in the elderly.

People with one copy of the mutant gene have about eight times the risk of age-related macular degeneration, or AMD, compared to people with normal genes. Having two copies — a condition found in about 5 percent of those studied — multiplies the risk 30-fold, said Kang Zhang, a professor of visual sciences at the University of Utah and lead researcher on the study published online Thursday in the journal Science.

"This is the gene that has by far the greatest genetic effect in both the Caucasian and Chinese population," Zhang said in a telephone interview, referring to the ethnic groups at greatest risk of the disease. "It explains about 50 percent of the genetic risk of macular degeneration."

The U. can already test patients to determine their risk, and other labs can easily conduct the test, said Paul Bernstein, another U. researcher who worked on the study. That will give patients a chance to add more antioxidants to their diets to help avoid the disease.

"It's clear that high doses of antioxidants such as beta carotene, zinc, vitamin C and vitamin E and fish oil are all important for lowering risk," he said in a telephone interview yesterday. People at genetic risk "are people we think should be making dramatic lifestyle changes if they haven't already."

Novartis AG and other companies produce drugs to inhibit the protein-destroying molecule, or protease, created by the gene, Zhang said. The drugs could potentially slow or stop AMD if they don't interrupt needed bodily functions, he said. Zhang said he has no financial relationship with drugmakers.

"We are in the process of all sorts of studies to see if any of the inhibition of this protein will affect AMD," he said. "They have a lot of off-the-shelf inhibitors that can be tried."

Macular degeneration afflicts almost 30 percent of people over age 75, the National Institutes of Health said on its Web site. AMD is more likely among women, smokers and the obese, the agency said. Patients with the disease can lose their central vision and often progress to legal blindness. Lucentis, a drug made by Genentech Inc., was approved in June to treat the condition.

Robert Bhisitkul, a professor of ophthalmology at the University of California, San Francisco, said identifying genes responsible for AMD could help researchers find treatments that work earlier than Lucentis. He wasn't involved in the study and is an unpaid adviser to Genentech.

Lucentis is for late in the disease, when "the house is already on fire," Bhisitkul said in a telephone interview yesterday. With genetic identification, it may become possible to intervene earlier and "prevent the house from catching on fire," he said.