Pigs with a genetic defect provide new perspectives for the treatment of Alzheimer’s

Cell Reports Medicine (2022). DOI: 10.116 / j.xcrm.2022.100740 “width =” 800 “height =” 530 “/>

Graphic abstract. Credit: Cell brings back the medicine (2022). DOI: 10.116 / j.xcrm.2022.100740

For decades, researchers around the world have worked hard to understand Alzheimer’s disease. Now, a collaboration between the Department of Biomedicine and the Department of Clinical Medicine at Aarhus University has resulted in a flock of piglets that could lead to a major breakthrough in Alzheimer’s research and treatment.

The cloned pigs are born with a mutation in the SORL1 gene, which is interesting because mutations are found in up to 2-3% of all early-onset Alzheimer’s cases in humans.

Due to the genetic mutation, pigs develop signs of Alzheimer’s at a young age. This gives researchers the opportunity to follow early signs of the disease, as pigs show changes in the same biomarkers used to make the diagnosis in humans.

“By following the changes over time in pigs, we can better understand the early changes in the cells. Subsequently, these changes lead to the irreversible changes in the brain that are the cause of dementia. But now we can track pigs before they manifest themselves. behavior, etc., which will allow testing of new drugs that can be used at an early stage to prevent SORL1-associated Alzheimer’s disease, “says Associate Professor Olav Michael Andersen, who is the first author of the study, just published in the scientific journal Cell brings back the medicine.

“Pigs resemble humans in many ways, which is why this increases the chances of producing drugs that work to fight Alzheimer’s. It’s important to have a viable animal model to bridge the gap between drug research and development,” he explains. .

Pigs cloned from skin cells

Since the 1990s, researchers have been aware of three genes that, if mutated, can directly cause Alzheimer’s disease.

Through intense research over the past 20 years, it has now been definitively established that a mutation in a fourth gene, namely SORL1, can also directly cause widespread dementia disorder. If this gene is defective, the person carrying the genetic defect will develop Alzheimer’s.

“We created an animal model for Alzheimer’s in piglets by modifying one of the four genes currently known to be directly responsible for the disease. Pigs can be used in the pharmaceutical industry to develop new drugs and, at the same time, this can provide researchers. better chance of understanding early changes in the brains of people who later develop Alzheimer’s, “says Olav Michael Andersen.

Researchers have also previously developed pig models for Alzheimer’s and other diseases using cloning. This is done by removing the hereditary material from an underused egg taken from a pig, after which the cell is fused with a skin cell from another pig.

In this study, the researchers had previously used CRISPR-Cas9-based gene editing to destroy the SORL1 gene in a skin cell taken from a piglet of the Göttingen breed.

The result is a reconstructed embryo, i.e. a cloned egg, which develops into a new individual with the same genetic characteristics as the genetically modified skin cell. This means that the cloned pigs are born with a damaged SORL1 gene.

“Pigs resemble Alzheimer’s patients who have defects in the SORL1 gene, in contrast to previous pig models for Alzheimer’s, which had one or more mutated human genes inserted in hopes of accelerating the disease,” says the associate professor. Charlotte Brandt Sørensen, who is responsible for the development of the genetically modified and cloned pigs.

As the mutation is inherited, researchers can now breed pigs that show the first signs of Alzheimer’s before they reach the age of three.

He can test medications before the disease breaks out

The study has important prospects, says Associate Professor Olav Michael Andersen.

“We know from human genetics that when the SORL1 gene is destroyed, we develop Alzheimer’s. We have shown that if we destroy this gene in pigs, the very first changes occur in the brain cells of the animals that we had dared to hope for. This allows us to find biomarkers that they reflect the early preclinical stage of the disease, “he says.

The Danish company Ellegaard Göttingen Minipigs owns the rights to the pig variety and is breeding them.

“The best thing would be to develop new drugs based on this porcine model, and we are well under way with preparations. The group of patients with SORL1 mutations is much larger than the group of patients who have errors in the other three known genes. “, says Olav Michael Andersen.

Researchers untangle the APOE4 gene, the most significant genetic risk factor for Alzheimer’s disease

More information:
Olav M. Andersen et al, A genetically modified minipig model for Alzheimer’s disease with haploinsufficiency SORL1, Cell brings back the medicine (2022). DOI: 10.116 / j.xcrm.2022.100740

Provided by the University of Aarhus

Citation: Genetically Defective Pigs Provide New Perspectives for Alzheimer’s Treatment (2022, September 22) Retrieved September 22, 2022 from https://medicalxpress.com/news/2022-09-pigs-gene-defect-perspectives -treatment.html

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