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Congo Red to the Rescue
23 January 2003 (All day)
A dye used for more than a century to stain autopsied brain tissue can prevent the devastating effects of Huntington's disease in mice, new research shows. The dye, called Congo red, breaks apart hallmark protein clumps in the brain, adding to evidence that these globs are to blame for symptoms of the disease.
In Huntington's disease, an inherited and fatal neurological disorder, proteins called huntingtin mass together in the brain and kill neurons. However, scientists have long debated whether the proteins themselves or primarily their aggregates cause the neurological decline characteristic of Huntington's. No existing treatments can slow the disease's progression, and most victims die by midlife.
Cell biologist Junying Yuan and her colleagues at Harvard Medical School in Boston were curious whether Congo red could break down aggregates of huntingtin. Other researchers had found hints in cultured cells that the commonly used dye could break apart proteins involved in related ailments such as Alzheimer's disease and prion diseases, and preliminary evidence suggested they might work against Huntington's. Yuan's team exposed human brain cells to Congo red between 6 and 48 hours after they began producing huntingtin. Adding the dye earlier caused a 60% decrease in cell death; adding it later reversed aggregation and prevented some damaging effects, like a loss of energy-producing ATP. Closer examination showed that Congo red forced protein aggregates to break apart.
The researchers then implanted a Congo red pump in the brains of genetically altered mice showing symptoms of Huntington's, such as weight loss and trouble walking. The animals' symptoms improved dramatically, though didn't disappear. They lived about 15% longer than controls, the group reports in the 23 January issue of Nature.
"Anything that has an effect on the toxicity is worth pursuing," says Kenneth Fischbeck, chief of the neurogenetics branch of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. Flint Beal, chair of neurology and neuroscience at Weil Medical College of Cornell University agrees, adding that he was impressed with Congo red's ability to break up aggregates. However, Fischbeck cautions, Congo red can't cross the blood-brain barrier, which may limit its use in humans.