INHIBITING KEY ENZYME SLOWS DOWN HUNTINGTON'S DISEASE PROGRESSION IN MICE

Emory University School of Medicine and Harvard Medical School scientists have discovered that an enzyme called caspase-1, found in the brains of humans and mice, may play a critical role in the progression of Huntington's disease. By inhibiting the enzyme, they have significantly delayed the progression of Huntington's disease in mice. The research is reported in the May 20 issue of Nature.

Huntington's is an inherited, progressive, neurodegenerative disorder that currently affects 30,000 Americans. The disease is characterized by movement disorders, psychiatric complications and dementia. An additional 150,000 individuals are at a 50% risk of inheriting the gene that is responsible for the disease. Huntington's causes the loss and dysfunction of specific kinds of neurons in the striatum and cortex of the brain.

Scientists used a transgenic mouse model that expressed the human Huntington's disease gene. The mice developed a progressive syndrome with many of the characteristics of human Huntington's disease. In order to evaluate a possible role for caspase enzymes in Huntington's disease, they crossbred the Huntington's mice with mice in which caspase-1 is inhibited by a gene mutation. Caspase-1 is responsible for helping trigger the death of brain cells.

The scientists found that in the crossbred mice, the onset of Huntington's disease was significantly delayed, and mouse life was extended by 20% when compared to mice without the inhibition of caspase.

"Our research showed not only that caspases have a novel role in cell death that relates to Huntington's, but also that they may play a role in cell dysfunction that leads to abnormal symptoms and eventually progresses to cell death," said Xiao-Jiang Li, Emory University assistant professor of genetics and one of the study's authors. "We expect our findings potentially to apply to human Huntington's disease as well."

The research was supported by grants from the Hereditary Disease Foundation and the National Institutes of Health.