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Small molecules might block mutant protein production in Huntington's disease
Date:5/3/2009

DALLAS May 3, 2009 Molecules that selectively interfere with protein production can stop human cells from making the abnormal molecules that cause Huntington's disease, researchers at UT Southwestern Medical Center have found.

These man-made molecules also were effective against the abnormal protein that causes Machado-Joseph disease, a neurological condition similar to Huntington's.

The work has been done only in cultured cells, and it will take years before the effectiveness of this process can be tested in patients, the researchers cautioned.

"I wouldn't want to give Huntington's patients or gene carriers any false hope, but I am excited about where this work might go in the future," said Dr. David Corey, professor of pharmacology and biochemistry at UT Southwestern and senior author of the study, which appears online May 3 in Nature Biotechnology.

The researchers' approach relies on interfering with the steps by which genetic information in cells is "translated" from DNA to make proteins, which carry out vital biological functions.

Huntington's and Machado-Joseph are fatal inherited diseases caused by abnormal repeats of a small segment in a person's DNA, or genetic code, represented by the letters CAG. These mutations result in the body producing malfunctioning proteins that cause the diseases. The more repeats, the worse the disease, and the earlier in life it appears. A person with the disease carries one normal copy of the gene and one mutated copy in his or her cells.

In Huntington's, this CAG repeat occurs in a gene called huntingtin, and in Machado-Joseph, it occurs in a gene called ataxin-3. A person with Huntington's can have up to 100 CAG repeats. CAG repeats are involved in several other neurodegenerative diseases, including Fragile X syndrome, the most common form of mental retardation, and myotonic dystrophy.

While these genes are best known for the devastating effects of
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

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