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Caltech researchers show efficacy of gene therapy in mouse models of Huntington's disease
Date:10/30/2009

Pasadena, Calif.Researchers at the California Institute of Technology (Caltech) have shown that a highly specific intrabody (an antibody fragment that works against a target inside a cell) is capable of stalling the development of Huntington's disease in a variety of mouse models.

"Gene therapy in these models successfully attenuated the symptoms of Huntington's disease and increased life span," notes Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences.

Patterson is the senior investigator on the study, which was published in the October 28 issue of the Journal of Neuroscience.

Huntington's disease is a neurodegenerative disorder with a genetic basis. The disorder has its roots in a mutation in a protein called huntingtin, or Htt. (The gene itself is also referred to as the huntingtin gene.)

All versions of the Htt gene have repeats of a particular trio of nucleotidesspecifically, C, A, and G, which together code for the amino acid glutamine. In most people, that trio is repeated between 10 and 35 times. But in people who develop Huntington's disease, that genetic stutter goes on and on; they will have anywhere between 36 to upwards of 120 repeats.

The result of all these repeats? An abnormally long version of the Htt protein, which gets chopped up into smaller, toxic pieces and accumulates in nerve cells, debilitating them.

Enter Patterson group members Amber Southwell and Jan Ko, who began to look at the efficacy of two different intrabodies that had been shown, in cell cultures and fruit-fly models, to reduce the accumulation of toxic Htt protein. To see whether those effects would hold true in mammalian systems as well, the team tested the intrabodies in a series of five different mouse models of Huntington's.

One of the two intrabodies had some negative results, actually increasing Huntington's-related mortality in one model.

But the other intra
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Contact: Lori Oliwenstein
lorio@caltech.edu
626-395-3631
California Institute of Technology
Source:Eurekalert

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