Huntington's Disease Linked to Overactive Immune Response in the Brain

by Rajashri on Jul 15 2008 4:23 PM

An over active immune response in the bloodstream and the brain may cause the same kind of damage to brain tissue as is seen in Huntington's disease, two research teams from the University of Washington in Seattle and University College London have discovered.

The two separate studies unearthed evidence in both brain cells and the bloodstream, suggesting an important link between the immune system's response and Huntington's disease.

Taken together, the findings resulting from the two studies may help scientists find biological markers for monitoring the disease progression earlier and with more accuracy, and also facilitate the development of new treatments for the disease.

Dr. Thomas Moeller, a neurologist who led the UW research team, said that their study revealed that patients with Huntington's had higher levels of immune-system signalling molecules, called cytokines, in their brain tissue.

His team later looked at a mouse-based model of the disease, studying the response of microglia, the immune cells of the nervous system.

When they treated the microglia with a molecule triggering an immune response, the microglia from Huntington's mice produced much higher levels of cytokines, the immune system molecules.

Moeller said that the finding suggested that the protein produced by the Huntington's disease genetic mutation, a protein called huntingtin, was causing the immune cells to be overactive.

The researchers said that overly strong immune response might be the mechanism through which the disease causes damage to neurons in the brain.

"When we found increased levels of cytokines in the brains of Huntington's disease patients, we were very excited. Inflammation in the brain has been increasingly recognized as an important component in other neurodegenerative diseases such as Alzheimer's or Parkinson's disease. These findings might open the door to novel therapeutic approaches for Huntington's disease that target inflammation," Moeller said.

On the other hand, researchers at University College London focused their work on immune cells in the bloodstream, and found similar results linking the disease to the body's immune response.

"The similar effect in the blood of Huntington's patients suggests that we have discovered a new pathway in the disease by which the mutant protein could cause damage. The protein could be causing damage through an abnormally overactive immune system in both the blood and the brain. While damage from Huntington's is typically seen in the brain, this new pathway is quite easy to detect in the blood of patients, so we may have found a unique window from the blood into what the disease is doing in the brain," Moeller said.

The immune response in the blood may also help researchers use immune-system molecules as biological markers for the disease, which can be difficult to diagnose in early stages.

Better tracking of Huntington's disease progression may help researchers to fine-tune interventions aimed at slowing the disease before it has affected as much brain tissue.

The findings of the two studies have been published in the Journal of Experimental Medicine.