Mini pig model may help scientists to better study late infantile Batten

Measuring changes in specific brain regions may also identify treatment response

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
An illustration of a brain with lightning bolts emanating from it.

A mini pig model could be an effective way to examine brain changes to track disease progression in late infantile Batten disease, a study suggests.

In addition, measuring changes in the size of specific brain regions may help identify response to potential treatments, researchers note.

“Miniswine present a valuable translational research tool for exploring and optimizing medical image acquisition and analysis, understanding disease etiology [development], and exploring innovative treatment options,” researchers wrote.

The study, “Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model,” was published in Scientific Reports.

Recommended Reading
An illustration of a group of mice.

Early data support Regenxbio’s gene therapy program for CLN2 disease

Researchers analyze patterns of brain damage progression in pig model

Late infantile Batten disease, also known as CLN2 disease, is caused by mutations that lead to the toxic build-up of waste molecules in brain cells, ultimately leading to progressive brain damage that drives disease symptoms.

In the study, a team led by scientists at the University of Iowa analyzed patterns of brain damage progression in a model of CLN2 disease using miniswine (miniature pigs), aiming to provide a baseline for future research using this model. The team noted that pigs are a particularly useful tool to study brain diseases because the shape and development of the pig brain is very similar to that of humans.

“Genetically modified miniswine can have standardized brain image acquisition times at pre-determined longitudinal timepoints, creating a more consistent representation of [CLN2] disease progression which is challenging to achieve in humans for rare pediatric diseases,” the researchers wrote.

They used MRI imaging to look at the brains of both diseased and wild-type pigs at 12 and 17 months, which respectively correspond to early and late stages in the progression of CLN2 disease in this pig model. The team specifically wanted to compare brain volumetrics — that is, the size of different brain regions.

The team noted that this study was limited only to female pigs, because “uncastrated male miniswine present additional challenges for longitudinal imaging and housing.”

Results showed that the total brain volume of CLN2 pigs was significantly smaller than their wild-type counterparts in early disease. Over time, wild-type pigs generally had a slight increase in brain volume, whereas brain volume declined further in CLN2 pigs.

Recommended Reading
Banner for

Grief fueling fury: What it means to fight Batten disease like a mother

Brain changes broadly similar to what’s seen in other neurodegenerative diseases

The proportion of the brain containing gray matter (the type of brain tissue housing the bodies of nerve cells) also was significantly lower in CLN2 than in wild-type pigs, whereas the amount of fluid in the brain was larger in CLN2 pigs, and these differences increased over time. Reduced areas of specific brain regions, namely the putamen and caudate, were also lower in CLN2 pigs. These patterns are broadly similar to changes that have been seen in other neurodegenerative diseases like Alzheimer’s disease, the researchers noted.

Taken together, the finding of measurable differences in brain regions that become more dramatic over time as the disease progresses “indicates that evaluation of MRI derived brain volumes could be utilized to monitor treatment response in preclinical miniswine studies,” the researchers concluded.

They suggested this pig model could be a useful way to study brain changes in Batten disease. However, using pigs has some disadvantages over other common laboratory animals like mice, the researchers noted, particularly in that it’s more expensive to house and care for the larger animals, in addition to the challenges in working with uncastrated male pigs.