New pig models of Huntington’s disease have been developed, and they are expected to have several benefits compared to existing rodent models of the condition. Read the source article here at HD Buzz, a website where scientists write accessible updates on Huntington’s disease research.
About Huntington’s Disease
Huntington’s disease is a genetic disease that affects the brain’s functioning. It can occur at any age, but often the first symptoms begin to appear between the ages of 30 and 50. Over time and as the condition progresses the symptoms become more severe, and the disease is often fatal.
People affected by Huntington’s disease might find that their memory and concentration worsen, or that they experience mood swings and/or depression. People may also develop jerking movements, poor coordination, and movement difficulties.
According to the NIH, Huntington’s disease affects between three to seven people of European ancestry out of every 100,000. The frequency is different for some other groups; for example, it is believed to be less common in people of Chinese, Japanese, and African descent.
Huntington’s Disease Animal Models
Since much of the damage caused by Huntington’s disease occurs in the brain, the condition is particularly difficult to take samples of and study in patients. To get around this problem, a lot of the research into the disease uses animal models, typically mice.
Although mouse models are key to a lot of the progress made by researchers studying Huntington’s disease, there are problems with this method. Mice and humans are, biologically, very different, and many of the phenomena seen in mice aren’t seen in humans, and vice versa.
The Pig Models
To provide an animal model more similar to humans, scientists from the Emory University and Jinan University’s Guangdong-Hongkong-Macau Institute of CNS Regeneration have used genetic editing techniques to create a pig model of Huntington’s disease.
They did this by putting the gene that causes Huntington’s disease in humans into pig skin cells, and then taking the nucleus (where the DNA is) from the cell and into a pig embryo. This embryo, which carried the Huntington’s disease gene, was then placed into a surrogate pig, who gave birth to a litter (technically known as a ‘drift’) of piglets that carried the Huntington’s disease gene.
Although there are some problems that arise with pig models as opposed to rodent models (such as higher costs, slower development, and smaller sample sizes), there are also several benefits to using this animal as a model.
Five Benefits of the Pig Model, According to Scientists
1. They are larger
The larger physical size of pigs compared to rodents is also a benefit for researchers. Some methods of treatment cannot be used on rodents due to their small size; for example, the experimental treatment ASO mediated HTT lowering, which has to be administered through a spinal injection, isn’t possible to carry out in smaller animals. In comparison, the larger physical size of pigs makes this kind of delivery method possible, meaning that they can be used to test a wider range of therapies.
2. The pigs’ movement symptoms are more similar to those of humans
One problem scientists working with rodent models of Huntington’s disease faced was that they did not develop movement difficulties commonly seen in human patients with Huntington’s disease.
In comparison, the new pig models do develop very similar movement issues (called chorea). Similarly to patients, as the pigs aged they were less able to walk and run. Scientists say that this means that they are more suitable than mice for testing new therapies on.
3. The pigs’ show brain changes typical of Huntington’s disease
In many people with Huntington’s disease, medium spiny neurons in the brain are damaged and die. This is believed to cause many of the early movement difficulties patients can experience. The pig models are similar to humans in that they also experience selective damage to this type of neuron.
4. Their brain immune response is also closer to that of a person’s
When the brain is damaged, certain cells are activated as part of the immune response (a process called gliosis), and this occurs in patients with Huntington’s disease. However, gliosis has not occurred in rodent models, but it has been shown to happen in the pigs.
5. They experience similar ‘knock-on’ effects to human patients
Huntington’s disease often becomes fatal for patients due to ‘knock-on’ effects from brain damage, such as breathing difficulties and pneumonia. According to HD Buzz, no other animal model of the condition has shown that type of knock-on effect, whereas the pig models do develop similar breathing problems, which the authors of the original article described as “groundbreaking.”
These new pig models of Huntington’s disease and their similarity to human patients are hoped to support further research into this area.