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June 23, 2008
‘Intrabody’ cleans up in Huntington’s disease model

By Quinn Eastman

Emory scientists have created a tool for mopping up the clumps of mutant protein that drive neurodegeneration in Huntington’s disease.

A team led by geneticist Xiao-Jiang Li engineered a virus to make an intracellular antibody or “intrabody” against huntingtin, the protein whose mutant forms poison the brain cells of people with the fatal inherited disease.

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 were published in the Journal of Cell Biology in May.

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 usually begins in young- to mid-adulthood with the destruction of brain cells and leads to involuntary movements and cognitive impairment. Disease-causing mutations lengthen 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 made of only one amino acid, called poly-glutamine, which makes the proteins clump together inside brain cells.