Stone emphasized that future searches for causative mutations of AMD must be painstaking in their precision and involve large numbers of patients. "It may well be that some of the variations we found in the other fibulin genes also cause AMD, but with our current analytical limitations, they are not detectable."

The researchers' next steps will include producing cell cultures and animal models that harbor the mutations identified in the NEJM study. These steps will help researchers determine whether the fibulin proteins do have an altered function that would produce AMD.

The discovery of the AMD-related mutations in the fibulin genes will open the way to exploring whether other components of the cellular machinery involving fibulins might be disrupted by mutations that cause AMD, said Stone.

"The most immediate clinical implication of these findings is that if we can use fibulin gene mutations to distinguish a particular group of AMD patients, we could imagine exploring whether they do better with a certain type of treatment than other AMD patients," he said. "Such distinctions are important, because pharmaceutical companies might already have a treatment that works for perhaps five percent of AMD patients. But if they treated a hundred patients with such a compound, they would conclude that it didn't work, because it wouldn't work for ninety-five percent of those patients."

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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
21-Jul-2004