Researchers at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin-Madison (UW) recently made a discovery that moves the scientific community one step closer to understanding and treating Parkinson’s disease. 

Parkinson’s, which affects more than 10 million people worldwide, progressively degrades the nervous system, causing tremors, loss of muscle control, cardiac and gastrointestinal dysfunction and other issues. The group at WiNPRC used gene-editing tools to introduce the disease’s most common genetic mutation into marmoset monkey stem cells and successfully reduce flaws in cellular chemistry. 

“We know now how to insert a single mutation, a point mutation, into the marmoset stem cell,” said Marina Emborg, professor of medical physics at UW. “This is an exquisite model of Parkinson’s. For testing therapies, this is the perfect platform.” 

The researchers used a version of the gene-editing technology CRISPR to change a single nucleotide—among more than 2.8 billion pairs—in the genetic code of the cells and give them a mutation called G2019S. 

In human Parkinson’s patients, G2019S causes over-activity of an enzyme called LRRK2, which is involved in a cell’s metabolism. Other gene-editing studies have seen cells produce both normal and mutated enzymes at the same time.  

This new study, however, is the first to result in cells that make only enzymes with the G2019S mutation, which makes it easier to study what role this mutation plays in the disease. 

“The metabolism inside our stem cells with the mutation was not as efficient as a normal cell, just as we see in Parkinson’s,” said Emborg. “Our cells had a shorter life in a dish. And when they were exposed to oxidative stress, they were less resilient to that.” 

The mutated cells had shorter life and were less resilient to oxidative stress. They also showed lackluster connections to other cells. Stem cells can develop into many different types of cells found throughout the body. But when the researchers spurred the mutated stem cells to differentiate into neurons, they developed fewer branches to connect and communicate with neighboring neurons. 

“We can see the impact of these mutations on the cells in the dish, and that gives us a glimpse of what we could see if we used the same genetic principles to introduce the mutation into a marmoset,” says Jenna Kropp Schmidt, a WiNPRC scientist and co-author of the study.  

The researchers also used marmoset stem cells to test a genetic treatment for Parkinson’s. They shortened part of a gene to block LRRK2 production, which made positive changes in cellular metabolism. 

“We found no differences in viability between (the altered cells) and normal cells, which is a big thing. And when we made neurons from these cells, we actually found an increased number of branches,” Emborg says. “This (particular technique) is a good candidate to explore as a potential Parkinson’s therapy.” 

To learn more about how scientists across the NPRC network are combating Parkinson’s disease and other neurological disorders, visit this link.