Scientists Discover Origins of Huntington's Disease in the Brain

Researchers may have uncovered the origins of Huntington's disease. They've used a unique approach to switch a gene mutation off in individual brain regions and zero in on those that play a role in causing the disease.

"From day one of conception, the mutant gene that causes Huntington's appears everywhere in the body, including every cell in the brain," said X. William Yang, one of the researchers, in a news release. "Before we can develop effective strategies to treat the disorder, we need to first identify where it starts and how it ravages the brain."

Huntington's disease is passed from generation to generation through a mutation in a gene called huntingtin. This mutation is a repetitive stretch of DNA at one end of the altered gene, and causes cell death and brain atrophy that progressively deprives patients of their ability to move, speak, eat and think clearly. Currently, no cure exists.

So how does this disease cause these symptoms? Huntington's disease targets cells in two brain regions for destruction, the cortex and the striatum. More neurons die in the striatum, but it's unclear whether cortical neurons play a role in the disease.

In order to find out a bit more about the disease, the researchers engineered a mouse model for Huntington's. They then integrated a "genetic scissors" that snipped off the repetitive DNA and shut down the defective gene. The researchers measured how the mutant gene influenced the disease development.

"The genetic scissors gave us the power to study the role of any cell type in Huntington's," said Nan Wang, one of the researchers, in a news release. "We were surprised to learn that cortical neurons play a key role in initiating aspects of the disease in the brain."

In the end, the researchers found that reducing huntingtin in the cortex partially improved the animals' symptoms. Not only that, but shutting down mutant huntingtin in both the cortical and striatal neurons, while leaving it untouched in the rest of the brain, corrected every symptom.

The findings shed light on where exactly Huntingon's disease starts. This, in turn, could allow scientists develop potential new treatments for the disease.

The findings are published in the journal Nature Medicine.