Hunting down clues to Huntington's

Finding a cure for any disease involves a long chain of events, starting with the identification of the disease, understanding its causes, and finally, developing a successful treatment. In the case of Huntington's disease, researchers know chunks of the chain, but some connective pieces — and a cure — remain elusive. One recent study is giving hope to better understand how some of those links fit together.

Drs. Andrew Strand and Jim Olson of the Clinical Research Division are co-authors on a study led by the Buck Institute for Age Research, published in the May 11 edition of PLoS Genetics, which explains important protein interactions that could lead to an effective treatment of the fatal disorder. The genetic mutation behind Huntington's disease is a protein that has changed shape and no longer interacts normally with other cellular proteins. "Knowing what the protein-protein interactions are is important for us to figure out this disease," Strand said. "The general idea of this study was to grind up various tissues to get a protein soup and pass that over the purified mutated protein that causes Huntington's to see what sticks."

In doing so, the researchers identified 234 proteins that bind to normal and mutant forms of the protein underlying Huntington's. They arbitrarily tested 60 of those proteins in a fly model, of which 27 were identified as high-confidence genetic modifiers. By expressing or suppressing the proteins, they were able to make conclusions about how to modify the effects of the protein that causes Huntington's disease, which could lead to an effective treatment. "So as opposed to taking 50 proteins from a random list, where you might find one or two genetic interacting proteins, almost all of these proteins have some genetic interaction in the fly system," Strand said. "These interactions are probably quite important to our understanding."

The National Institutes of Health and the Hereditary Disease Foundation funded the study. Future studies are planned that involve categorizing the proteins described in the paper.