In a new approach, scientists at the University of California, San Francisco have sought to treat Alzheimer’s disease using new technology. The approach is to focus on microglia, a cell type that stabilizes the brain by shedding damaged neurons and proteins that are often associated with dementia and other brain diseases. While changes in these cells have been linked to Alzheimer’s disease, they remain to be understudied. The researchers have now used a new CRISPR technology that allows them to control these microglia cells. This, according to the team, may lead to a new approach to the treatment of Alzheimer’s disease.
In the brain, ordinary immune cells cannot cross the blood-brain barrier. This is where microglial cells come in. They act like the brain’s immune system and help eliminate waste and toxins while keeping neurons functioning properly. When these microglial cells begin to stray, it leads to inflammation in the brain and can damage neurons and their networks.
Microglia cells can even end up suppressing synapses between neurons under certain conditions. This process is part of normal brain development during childhood and adolescence. But, in adults, it can have disastrous effects on the brain.
The team, led by Martin Kampmann, PhD, set out to detect genes responsible for specific states of microglial activity. With this, they could switch genes on and off and put dislodged cells back in their place.
They made microglial cells from stem cells donated by human volunteers and confirmed that they worked like their regular human counterparts. The team then set out to develop a new platform that combines a form of CRISPR and allows researchers to switch individual genes on and off.
Thanks to this, the team was able to focus on the genes responsible for the cell’s ability to survive and proliferate. Genes have also impacted the activity with which a cell produces inflammatory substances and the aggressiveness with which a cell prunes synapses. Detecting the type of genes helped the researchers to successfully rest them and convert the disease-infected cell into a healthy one.
“Our study provides a model for a new treatment approach,” he said. “It’s kind of the holy grail,” Kampmann said. He is the lead author of the study published in Natural neuroscience.