Genetic mutation linked to illness that blinds millions

Friday, March 11th 2005, 8:35 am

By: News On 6

WASHINGTON (AP) _ A gene mutation has been linked to age-related macular degeneration, the leading cause of blindness in the elderly, by three sets of researchers working independently.

An estimated 15 million Americans suffer from the disorder, a number expected to double as the baby boom generation ages.

Being able to relate a gene mutation to the likelihood of developing the illness may lead to better tests and eventually treatments, the scientists hope.

``I don't think it's going to be a year or two ... but I'd guess less than 10 years'' before a treatment might become available, said Albert O. Edwards, the lead researcher for one group of researchers reporting on the link.

In cases of macular degeneration the central region of the eye's retina deteriorates, damaging or destroying vision. There are no broadly effective treatments, though a recently approved drug can slow the disease for some patients.

The new gene findings are reported in separate papers in this week's online issue of the journal Science. The research groups were led by Edwards, at the University of Texas Southwestern Medical Center, Josephine Hoh of Yale University School of Medicine and Margaret A. Pericak-Vance of Duke University Medical Center.

The teams studied the genes of people with AMD and others without the disease and found that people with a variation in the CFH gene were more likely to have the illness. The gene is involved in the production of a protein called complement factor H that helps regulate inflammation in a branch of the immune system.

According to the Texas-based researchers, as many as half of AMD cases in the elderly could be related to the gene variant.

Edwards, now the president of the Institute for Retina Research at Presbyterian Hospital of Dallas, noted that risk factors for AMD are similar to those for cardiovascular illness, including obesity, lack of exercise and smoking.

``There is an unexplained increased risk of cardiovascular mortality in people with AMD,'' he said. ``This may actually go beyond eye disease ... those studies have to be done.''

Pericak-Vance, director of the Duke Center for Human Genetics, said her study indicated that the gene variant could account for about 43 percent of the risk of developing AMD for older adults.

``This gene opens the door to a whole new understanding of the factors that contribute to this disease,'' she said in a statement. ``The finding may ultimately lead to new methods for identifying those at high risk for macular degeneration and suggests new pathways for drug development.''

Hoh, an assistant professor in the Department of Epidemiology and Public Health at Yale, reported that ``Caucasian AMD patients are at least four times more likely to have one particular alteration in the CFH gene that produces a different form of the CFH protein, compared to individuals without the disease.''

Dennis Schultz of Oregon Health and Science University, who two years ago identified a different gene involved in some cases of AMD, said the studies are an important finding, though not yet the whole story.

``It's complex, very difficult to understand, there are many genes involved and the environment plays a role as well,'' said Schultz, who was not part of the three study teams.

There are two forms of macular degeneration. The more common ``dry'' form progresses relatively slowly. The less common ``wet'' form, involving bleeding in the eye, can destroy vision rapidly. Both forms were associated with the CFH gene variation.

In December the Food and Drug Administration approved the drug Macugen for treatment of the wet form of AMD. In studies untreated patients had about a 45 percent chance of significant vision loss in a year compared with 30 percent for patients on Macugen. In addition, supplements including zinc and vitamins E, C and A have been shown to help some AMD patients.

The researchers was funded by the Raymond and Beverly Sackler Fund for the Arts and Sciences, the National Eye Institute, the National Institute on Aging, the National Center for Research Resources and Research to Prevent Blindness.