Scientists at Yerkes National Primate Research Center, Emory University have shown that transgenic monkeys for Huntington’s disease exhibit early emergent symptoms, like humans with the disease, which bolsters the idea that monkeys could be effective animal models for developing therapies.
The study, “Increased irritability, anxiety, and immune reactivity in transgenic Huntington’s disease monkeys,” was published in the journal Brain, Behavior and Immunity.
“Identifying emotional and immune symptoms in the HD monkeys, along with previous studies demonstrating their cognitive deficits and fine motor problems, suggest the HD monkey model embodies the full array of symptoms similar to human patients with the disease,” study author Jessica Raper, PhD, said in a press release.
In 2015, researchers used Rhesus macaques carrying a gene that encoded a fragment of the mutant human huntingtin protein, to study the human features of the disease. They observed the animals suffered from dystonia (uncontrollable and sometimes painful muscle spasms caused by incorrect signals from the brain) and fine motor impairment at two and three years old, respectively.
In the recent study, Emory researchers investigated emotional and immune symptoms in two Huntington’s disease monkeys, both five years old. The animals were exposed to acute stress created by the presence of an unfamiliar human. Typically, monkeys are expected to change their behavior according to the level of threat: “no threat” is when the animal is alone in the room; “mild threat” occurs upon the presence of an unfamiliar human who avoids eye contact; and “high threat” occurs when the human makes direct eye contact with the animal.
Scientists detected that Huntington’s monkeys had no ability to distinguish the three threat differences and displayed “species typical” hostility during all conditions. This behavioral profile is akin to increased irritability, a common early Huntington’s symptom displayed by human patients before any signs of motor symptoms.
“Before our work in rhesus monkeys, it has not been possible to detect or observe some of these symptoms in other HD animal models, especially emotional dysregulation,” said study author Anthony Chan, PhD. “This will strengthen preclinical investigations of treatments in the HD monkeys.”
Huntington’s monkeys also showed changes in the immune system, including high levels of inflammatory markers in the blood (cytokines and inflammatory pathway genes). The alterations represent potential therapeutic targets for future clinical research.
The authors wrote: “Future studies will follow the emotional behavior development from infancy to adulthood in a new generation of HD monkeys to confirm whether increased anxiety and irritability is the result of brain or motor behavior changes.”