Potential Treatment For Huntington's Disease
 Investigators have found that normal synaptic activity in nerve cells protects the brain from the misfolded proteins associated with Huntington's disease.
In contrast, excessive extrasynaptic activity (aberrant electrical activity in the brain, usually not associated with communication between nerve cells) enhances the misfolded proteins' deadly effects.
Researchers also found that the drug Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity. The research was published in the journal Nature Medicine on November 15.
Huntington's disease is a hereditary condition caused by a mutated huntingtin gene that creates a misfolded, and therefore dysfunctional, protein. The new research shows that normal synaptic receptor activity makes nerve cells more resistant to the mutant proteins. However, excessive extrasynaptic activity contributed to increased nerve cell death.
The research team found that low doses of Memantine reduce extrasynaptic activity without impairing protective synaptic activity.
The work was led by Stuart A. Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neuroscience, Aging and Stem Cell Research at Burnham and professor in the department of Neurosciences and attending neurologist at the University of California, San Diego and Michael R. Hayden, M.D., Ph.D., University Killam professor in the department of Medical Genetics at UBC and director of the Centre for Molecular Medicine and Therapeutics at the Child & Family Research Institute.
"Chronic neurodegenerative diseases like Huntington's, Alzheimer's and Parkinson's are all related to protein misfolding," said Dr. Lipton. "We show here, for the first time, that electrical activity controls protein folding, and if you have a drug that can adjust the electrical activity to the correct levels, you can protect against misfolding.
Also, this verifies that appropriate electrical activity is protective, supporting the 'use it or lose it theory' of brain activity at the molecular level. For example, this finding may explain why epidemiologists have found that 'using' your brain by performing crossword puzzles and other games can stave off cognitive decline in diseases like Alzheimer's."
Source: Burnham Institute
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