October 26, 2006
Research links Huntington’s disease to metabolic defects
Huntington’s disease includes a metabolic disorder, not just the brain effects seen in the disease, according to a new study by University of Washington researchers. The study appears in the November issue of the journal Cell Metabolism.
Huntington’s has long been considered simply a neurodegenerative disease. But a group of researchers led by Albert R. La Spada, associate professor of laboratory medicine, medicine and neurology, has found evidence of ties between the neuron loss caused by the disease and a defect in the metabolic system. The link would explain other symptoms of the disease, such as weight loss.
The disease causes the loss of neurons in the striatum, a region of the brain responsible for movement control. That degeneration causes the uncontrollable dance-like movements seen in Huntington’s patients. The genetic disease is fatal, with patients often succumbing to the disease in 10 to 25 years after its onset.
La Spada, who is also director of the UW Center for Neurogenetics and Neurotherapeutics, and his colleagues discovered the metabolic system connection after realizing that mice with an animal-model version of Huntington’s disease had extremely low body temperatures that drop even lower as the disease progresses.
They found that a gene involved in body-temperature control was failing to cause the events that help maintain a stable temperature.
They also found that other genes related to that body-temperature gene were exhibiting much lower activity in the striatum tissue, where Huntington’s disease causes neurons to die off.
That connection indicates that the metabolic problems and the neurodegeneration are likely related.
That connection also links two previous theories on Huntington’s disease. Some evidence suggested that the energy-producing mitochondria in cells may play a role in the disease, since the striatum is so sensitive to mitochondrial dysfunction.
Other research on the disease has suggested that the mutant gene that causes Huntington’s might interfere with gene transcription factors, which control the activity of other genes.
