August 25, 1997
Volume 50, No. 1
Emory researchers are helping to unravel the mystery surrounding Huntington's disease, the devastating inherited illness that caused the death of folk singer Woody Guthrie. Some of their findings, which were published recently in the Journal of Neuroscience, show that a mutated protein from a mutated gene kills nerve cells in the brains of those with Huntington's disease.
"This is the first paper that actually connects the level of mutant protein to susceptibility to neuron death," said senior author Steven Hersch, assistant professor of neurology at the School of Medicine.
Huntington's disease is a genetic illness that usually starts in midlife, although it may appear in infancy or old age. It's characterized by dementia and involuntary jerking or writhing movements-called chorea-and usually starts out with mild symptoms, becoming progressively worse over a course of 15 to 25 years and eventually resulting in death.
In the United States, an estimated 35,000 people have been diagnosed with Huntington's disease, and about 150,000 others carry the gene and will probably develop the disease. A child born to someone carrying the Huntington's gene has a 50 percent chance of inheriting it.
What distinguishes Huntington's from other neurodegenerative diseases such as Alzheimer's is the populations of neurons that die, Hersch explained. In Huntington's, these neurons are located in the striatum-the part of the brain's basal ganglia that controls movement and emotions.
In recent years, scientists have made significant progress toward understanding this illness. In 1993, researchers discovered the gene that's associated with Huntington's disease-gene IT15, located on chromosome 4.
And in 1995, several groups of researchers, including Hersch's team at Emory, identified "huntingtin," the normal protein that is expressed by this gene. They also determined that a mutant form of this protein may be produced by a mutant gene.
"Most of the papers published in 1995 suggested that huntingtin protein was basically in all the neurons of the brain, and therefore the presence of huntingtin did not predict which neurons of the brain died and which didn't," Hersch said.
Hersch and his research associates doubted that theory and began to look at brain tissue from cadavers of people without Huntington's to see which neurons had high levels of huntingtin protein and which had low ones. This recently published study found "that the cells that died the quickest have the highest levels of huntingtin, and the cells that were preserved in the brain have little or no huntingtin," Hersch said.
His research team's next goal is to discover the normal function of huntingtin and how alteration in the protein caused by genetic mutation changes the normal function of the protein, Hersch said. "We're trying to understand what it is about this abnormal huntingtin protein that does kill cells," he said. "Now that we know its mission is to kill cells, we want to know how it does that so that we can find treatments."
Hersch noted that other Emory researchers also are working on this problem, including Tim Greenamyre in the Department of Neurology, and Xiao-Jiang Li in the Department of Genetics.
Hersch also directs the Emory Huntington's Disease Clinic at Wesley Woods, a regional clinic that provides care and genetic testing for families with a history of the disease. The clinic will be taking part in a federally sponsored, multicenter trial of two new drugs. "Hopefully, these drugs will slow down or halt the progression of the disease," Hersch said.
The Huntington's Disease Society of America also has named Emory the first Center for the Care and Cure of Huntington's. The society's funding will help the clinic take care of individuals with Huntington's and will support more research.
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