July 20, 1997

Media Contacts: Sarah Goodwin, 404/727-3366 -
Kathi Ovnic, 404/727-9371 -

The first compelling explanation of why some populations of nerve cells (neurons) degenerate during the progression of Huntington's disease while others are immune reported Emory researchers in a recent issue of Journal of Neuroscience.

"For the first time, the pattern of brain cell loss which occurs in Huntington's disease has been linked to the Huntington's disease genetic mutation," says senior author Steven M. Hersch, M.D., Ph.D., assistant professor of Neurology at the Emory University School of Medicine. "Simply put, we studied normal human brain and found that the Huntington's disease gene product, huntingtin, is expressed in high levels in the neurons that die and at low levels in the neurons that resist degeneration. Previous studies of huntingtin expression had implied that it is ubiquitous in neurons."

The team of researchers from Emory, Boston University and Harvard conducted tests on cadaveric brain tissue of 12 adults who died of causes other than neurological disorders. Using three different huntingtin antibodies to examine the immunoreactivity of striatal brain cells, the group found distinct differences in levels of immunoreactivity to huntingtin. They then used other markers to determine whether the brain cells with high or low levels of huntingtin expression correspond to the brain cells known to be vulnerable or resistant to degeneration in Huntington's disease.

"These observations suggest that the selective vulnerability of spiny striatal neurons and the matrix compartment observed in Huntington's disease is associated with higher levels of huntingtin expression, whereas the relative resistance of large and medium-sized interneurons and the patch compartments to degeneration is associated with low levels of huntingtin expression," the authors report.

Dr. Hersch explains that these observations are particularly relevant to the understanding of Huntington's disease because they provide the first simple explanation of why some neurons degenerate and others do not. Since higher dosages of mutant huntingtin within brain cells thus appear to be more toxic than lower doses, modulation of huntingtin itself might provide a treatment.

Co-authors of the paper include the following: first author Robert J. Ferrante and Neil W. Kowall of the Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Bedford, Mass., and Neurology Department, Boston University School of Medicine; Claire-Anne Gutekunst, Department of Neurology, Emory; Francesca Persichetti, Sandra M. McNeil, James F. Gusella and Marcy E. MacDonald of Molecular Neurogenetics Unit, Massachusetts General Hospital; and M. Flint Beal of the Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School.

The gene associated with Huntington's -- named IT15 and located on chromosome 4 -- was discovered in 1993. Two years later, several groups, including Dr. Hersch's Emory team, identified and localized huntingtin, the protein expressed by the Huntington's gene and determined that the mutant protein is produced. The function of huntingtin is not yet known, although identification of some of the proteins with which it interacts is beginning to provide some clues, Dr. Hersch says.

Huntington's disease is an inherited disorder characterized by jerky, involuntary movements called chorea, and progressive dementia -- all caused by the progressive and selective loss of brain cells in the basal ganglia and other regions of the brain. Symptoms usually do not become apparent until the third to fifth decades of life. Children of carriers of the Huntington's disease gene have a 50 percent chance of inheriting the gene. Genetic testing now is available to confirm the presence of the gene.

The study was supported by Huntington's Disease Society of America, Department of Veterans Affairs, Emory University Research Committee, Huntington's Disease Foundation and National Institutes of Health.

For more general information on The Robert W. Woodruff Health Sciences Center, call Health Sciences News and Information at 404-727-5686, or send e-mail to

Copyright ©Emory University, 1997. All Rights Reserved.
Send comments to