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'Intrabody' can mop up mutant protein in Huntington's disease model
Date:5/25/2008

Scientists have created a tool for mopping up the clumps of mutant protein that drive neurodegeneration in Huntington's disease. Emory University researchers engineered a virus to make an intracellular antibody or "intrabody" against huntingtin, the protein whose mutant forms poison the brain cells of people with Huntington's.

Injecting the virus into the brains of mice that make mutant huntingtin improves their ability to move their limbs, although it does not prolong their lives.

The results will be published online and are scheduled for publication in the May/June issue of the Journal of Cell Biology.

Although other researchers have shown that various intrabodies can protect cells from mutant huntingtin, the Emory team was the first to examine the effects of an intrabody in living mice, says senior author Xiao-Jiang Li, PhD, professor of human genetics at Emory University School of Medicine.

Delivering the intrabody to brain tissues in people would be a formidable challenge, because it would require some form of gene therapy. However, it may be possible to use information about the intrabody's structure to find drugs that mimic its effects, Li says.

Huntington's affects about 30,000 people in the United States and usually begins in young- to mid-adulthood with the slow destruction of brain cells, leading to involuntary movements, cognitive impairment and sometimes depression or paranoia. Another 150,000 people are believed to have mutations that cause the disease, but have not begun to show clinical symptoms. The disease is fatal and currently there is no way to slow its development, although some medications can alleviate symptoms.

Disease-causing mutations involve a lengthening of part of the gene for huntingtin, so that it repeats three letters (CAG) of the genetic code dozens of times. Mutant proteins have a region consisting of the same amino acid (glutamine) many times, called poly-glutamine, which
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

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