DURHAM, N.C. -- As reported in the March issue of Nature Medicine, Duke University Medical Center researchers have found a possible key to brain disorders such as Huntington's disease, as well as discovering a new concept of how mutant genes may produce disease.

The scientists discovered that these "triplet repeat" disease genes produce proteins that errantly stick to an enzyme crucial to the production of energy in brain cells. They believe that because this enzyme cannot, therefore, do its job, brain tissue will malfunction and may, over years, die. This would result in fatal physical and intellectual deterioration, such as that seen in Huntington's disease patients.

Furthermore, their findings may answer why the number of genetic repeats in these diseases determines how severe symptoms will be: More repeats produce a protein that holds this "energy" enzyme more tightly, producing widespread nerve cell failure in the brain.

The work offers biomedical researchers a new way to understand, and to potentially treat these genetic diseases, the Duke scientists say.

"This is the first explanation of what these proteins produced by triplet repeat genes may be doing in nerve cells," said neurologist and principal investigator Dr. Warren Strittmatter. "It provides a new paradigm for inherited neurologic disease, and that is the repeat region of these proteins binds other proteins critical to glucose and oxygen metabolism in the brain. And the larger the repeat region, the tighter they bind."

Authors of the study are from the same team that discovered the major gene linked to Alzheimer's disease. In many ways, "this finding may be more pivotal than our earlier work," said Dr. Allen Roses, scientific director of the Deane Laboratory at Duke, where the experiments were conducted. "We are beginning to cross the difficult area between gene discovery and abnormal functions of the brain, and to open the door to target drugs," he
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Contact: Renee Twombly
twomb001@mc.duke.edu
919-660-1313
Duke University
29-Apr-1996