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Berkeley Lab scientists help develop promising therapy for Huntington's disease
Date:11/1/2012

and tested the mice's motor skills. In one test, the mice were placed on a spinning rotarod, which forces them to balance like a lumberjack at a log rolling competition. The non-treated Huntington's mice performed progressively worse as they aged. The XJB-treated Huntingon's mice performed as well as normal mice over the same period.

In another test, grip strength was measured by prompting the mice to hang on a bar for 30 seconds. Almost all of the non-treated Huntington's mice failed the test, while 85 percent of the XJB-treated Huntington's mice passed the test. The treatment also stopped weight loss in Huntington's mice, which is another hallmark of the disease.

"We saw improvements across the board. The difference was amazing. XJB prevented the onset of weight loss and the decline in motor skills," says McMurray.

Next, the researchers removed neurons from the Huntington's mice and cultured the cells in the presence of XJB-5-131. They found that XJB-5-131 significantly improved the survival of neuronal cultures compared to untreated neuronal cultures.

Xun and colleagues also studied the impacts of the compound on the mice's mitochondrial DNA. They discovered that XJB-5-131 dramatically lowered the number of lesions on the DNA, which is a sign of oxidative damage. They also tallied the number of mitochondrial DNA copies, which plummets in diseased mice. This number was restored back to normal in XJB-treated mice.

In addition, Xun isolated nerve terminals from the Huntington mice's striatum and cerebral cortex, two parts of the brain that are affected by Huntington's disease. She found that XJB-5-131 significantly improved the ability of the mitochondria within these nerve terminals to respond to stress.

She also exposed mitochondria to a chemical that induces the formation of reactive oxygen species. As expected, this impaired mitochondrial function. But when the chemical was used along with XJB-5-131, mitoch
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Contact: Dan Krotz
dakrotz@lbl.gov
510-486-4019
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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