Huntington's study focuses on calcium levels-Abnormally high amounts may kill nerve cells
Abnormal calcium levels may be killing brain cells in people with Huntington's disease, a new study by Dallas researchers suggests.
More studies are needed to confirm the idea, but if it's right, the findings could offer new ideas for preventing or treating the fatal neurological disorder.
People with Huntington's disease have emotional and mental difficulties, as well as poor coordination. As the disease progresses, concentration and memory deteriorate along with the ability to walk, talk or swallow. Death occurs from complications such as choking, infection or heart failure.
The disease develops when someone inherits a faulty gene from either parent. Somehow, the abnormal gene causes certain brain cells to die when the person nears middle age.
In the new study, scientists at the University of Southwestern Medical Center at Dallas showed that the abnormal gene causes calcium levels to be unusually high in nerve cells. The study, released Wednesday, appears in the latest issue of the journal Neuron.
Abnormally high calcium levels may be important in the disease, said UT Southwestern's Ilya Bezprozvanny, because other studies have linked high calcium to nerve cell death.
Until now, he said, "this has never been proposed in Huntington's disease."
Dr. Bezprozvanny and his colleagues at UT Southwestern and the University of British Columbia in Vancouver discovered that a brain protein known to regulate calcium levels links up with a second protein made by the gene that causes Huntington's. Under normal circumstances, the two proteins help nerve cells maintain the correct calcium levels for triggering many brain cell processes, Dr. Bezprozvanny said.
But in Huntington's disease, the gene is abnormal, and therefore, so is the second protein. In the new study, the scientists noticed that in nerve cells grown in lab dishes, the abnormal protein caused calcium levels to rise too high.
The next step, Dr. Bezprozvanny said, is to study mice that carry the abnormal Huntington's disease gene. As in Huntington's patients, brain cells die in these mice, and the researchers want to see if restoring calcium levels will prevent the cells' death.
"If we are right," Dr. Bezprozvanny said, "it should spare the neurons from degeneration."
These studies should take about a year, he said. If they go as hoped, more studies would have to be done to see if the same approach could help patients with Huntington's.
Other researchers praised the study because it offers solid hope for scientists trying to crack Huntington's disease. Scientists have known of the gene abnormality for years, said Barbara Ehrlich, a cell biologist at Yale University School of Medicine in New Haven, Conn. But, she said, it has been difficult to go beyond that.
"One of the things that makes this piece so interesting is they push it one step further to what is happening in a cell to cause this disease," said Dr. Ehrlich, who wrote a commentary about the new work in the same issue of the journal. "It seems plausible, and it has more than an average chance of being correct."
One mystery in Huntington's disease is why only some cells in the brain die. Dr. Bezprozvanny said that the proteins he studied are particularly active in the cells that die in Huntington's patients. This could explain why other brain cells continue to live normally, he said. Other theories about the cause of brain cell death haven't been able to explain why only some cells die.
Other UT Southwestern researchers involved in the study were Tie-Shan Tang, Huiping Tu, Edmond Chan, Anton Maximov and Zhengnan Wang.
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