Yerkes’ monkey business

Researchers develop first transgenic nonhuman primate model of Huntington’s disease

Jeffrey Bouley
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ATLANTA—Trying to edge closer to an animal model that will more accurately predict human responses, researchers in the Yerkes National Primate Research Center at Emory University, in collaboration with researchers from the Department of Human Genetics at Emory's School of Medicine, have developed the first transgenic nonhuman primate model of the neurodegenerative condition known as Huntington's disease.

Reportedly the first study of its kind, this work is expected to lead to greater understanding of the underlying biology of Huntington's and to the development of potential therapies. The study was supported by a grant from the NIH and results were published in the May 18 advance online publication of Nature.

The progress isn't likely to stop with Huntington's, of course, and lead researcher Dr. Anthony W.S. Chan, an assistant research professor at the Yerkes Research Center and an assistant professor in the Department of Human Genetics, says this primate model will lead the way toward the development of other nonhuman primate models—and ideally in other primates in addition to rhesus macaques—for a variety of diseases.

"Alzheimer's disease is another serious neurodegenerative disease that would be likely to come forward soon in a transgenic primate model, as is Parkinson's disease," Chan says. "That's not the end of it for neurodegenerative diseases, though, and this success offers promise for non-neurodegenerative diseases as well, but Alzheimer's and Parkinson's are the short-term areas most likely to see development."

A transgenic primate model is a huge step forward for accurately gauging how Huntington's progresses in humans and how it responds to treatment, Chan notes.
"In the past, researchers have used transgenic mouse models to study the disease," he says. "These models do not completely parallel the brain changes and behavioral features observed in humans with Huntington's, thus making the development of a transgenic nonhuman primate model critical to currently treating and ultimately preventing the disease."
In creating this transgenic model, Chan and his colleagues have so far focused on fairly broad characterizations of Huntington's in the rhesus monkeys. Next steps include going into more detail using MRIs, genomic and proteomic profiles, and other technologies to confirm that the disease tracks in a similar way as in humans. If it turns out to be as good a model as it seems so far, Chan says the next challenge will be to figure out how to increase the number of animals produced so that they can meet the demands of drug discovery and development researchers, as well as possibly explore other primates for similar use.

"The transgenic monkeys are providing us with unparalleled opportunities for behavioral and cognitive assessments that mirror the assessments used with humans," Chan says. "With such information, much of which we are obtaining by using the Yerkes Research Center's extensive imaging capabilities, we are developing a more comprehensive view of the disease than currently available."

"This study is a complement to the many neuroscience programs at Yerkes and further solidifies our role at the forefront of neuroscience research," said Dr. Stuart Zola, director of the Yerkes Research Center—and the study's co-investigator leading the behavioral assessments—in a news release about the research. DDN

Jeffrey Bouley

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