Drug treatment promising for halting Huntington's-related nerve death

DALLAS Jan. 31, 2005 Researchers at UT Southwestern Medical Center have discovered that drugs commonly used to treat psychiatric illnesses and blood disorders in humans may protect the brain cells that die in people with Huntington's disease, possibly delaying the onset and slowing the progression of the disease.

These findings, available online and in today's issue of Proceedings of the National Academy of Sciences, may offer new treatment options for Huntington's disease, which has no cure.

Huntington's disease is a neurological disorder in which the medium spiny striatal neurons, the nerve cells that control movement and certain mental functions die. Patients die within 10-15 years after onset of the disease.

The disease is caused by a mutation in the gene that makes the protein huntingtin. The mutation creates a long chain of the amino acid glutamine at one end of the protein. The length of the chain directly correlates with age of onset of the disease, with longer chains leading to symptoms earlier in life.

In previous studies, Dr. Ilya Bezprozvanny, associate professor of physiology at UT Southwestern, established that one of the defects that leads to death of nerve cells with the mutant huntingtin protein is improper regulation of calcium due to errant signals in the cells. Calcium is inappropriately released from its storage area in the cells, and eventually the cells die.

"We have developed a model that links the mutation in huntingtin with degeneration of motor neurons," Dr. Bezprozvanny said. "The model connects all the dots between the Huntington's disease mutation, defective calcium signaling in the cell, and subsequent degeneration of medium spiny striatal neurons."

In the current study, using the medium spiny neurons of mice that carry a copy of the mutated human huntingtin gene, Dr. Bezprozvanny and colleagues found that treatment of the cells in culture with the drug enoxaparin prevented inappropriate calciu

Contact: Megha Satyanarayana
UT Southwestern Medical Center

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