Mini Pig Model May Be Useful for Assessing Huntington’s Symptoms, Progression, Study Suggests

Analysis of behavior patterns in genetically engineered mini pigs could be a valuable tool for assessing Huntington’s disease symptoms, a study shows.

This new animal model may help researchers further explore the progression of the disease, as well as daily symptom fluctuations and new strategies to manage them.

The study, “Activity Behaviour of Minipigs Transgenic for the Huntington Gene,” was published in the Journal of Huntington’s Disease.

Huntington’s disease is characterized by motor, cognitive, and behavioral symptoms caused by a mutated version of the huntingtin protein (mHTT). Many patients often experience sleep problems that can have a big impact on their quality of life and lead to serious alterations in their daily routines.

In addition, several studies have suggested that changes in behavior, including loss of initiative, low perseverance, irritability, and anxiety, are some of the earliest symptoms of Huntington’s disease. Consequently, these could be a promising target for early treatment.

Assessing behavioral disruptions in animal models may be a good marker for research that can be translated from the lab to the clinic, with early and reliable detection of behavioral changes helping to assess the effects of potential treatments.

Mini pigs have a genetic landscape that is very similar to humans, in addition to widely recognized anatomic and metabolic similarities. This makes the animals a very attractive preclinical model to study human disorders, in particular for the neuroscience field, which has few reliable and accurate preclinical models.

Researchers at the George-Huntington-Institute in Germany explored the potential of using Libechov mini pigs as a model for Huntington’s disease behavioral changes. They compared the daily behavior patterns of animals genetically modified to express the mutant HTT protein with that of healthy mini pigs.

Both groups were inactive most of the time, spending an average of 79.9% of their time resting or just standing. An hourly analysis revealed that the animals were more active between 9 a.m. and 5 p.m.

The researchers found that, during this period of the day, there was a significant difference in the activity pattern of the two groups, with Huntington’s mini pigs spending less time resting or standing between 10 and 11 a.m. Huntington’s mini pigs also tended to be more active at 4 p.m.

Between 9 a.m. and 6 p.m., there were also some differences regarding the time spent with litter. At 10 a.m. and 1 and 4 p.m., Huntington’s mini pigs spent significantly more time with rooting activities, showing more frequent occupation with litter.

Huntington’s mini pigs were found to walk an average of 1.5 times farther per day than healthy animals. However, there were fewer animals available to assess the distance covered, preventing researchers from confirming the statistical relevance of this observation.

These results demonstrate that “activity behavior may be a viable marker for [assessing] minipigs transgenic for the Huntington gene,” the researchers wrote. “Video recordings of behavioral patterns provide a non-invasive opportunity to capture potential disease signs.”

These animals may also represent a relevant preclinical model to explore the symptoms and understand the underlying biological processes of more advanced Huntington’s disease, they suggested.