According to new research, the discovery of how to shift damaged brain cells from a diseased state to being healthy, holds the potential of being a new treatment for Alzheimer’s.
The focal point of the research is on microglia – the cells that stabilise the brain by clearing out damaged neurons and the protein plaques often associated with dementia and other brain diseases.
At this current time, these cells are understudied, despite playing a significant role in Alzheimer’s and other brain diseases, according to senior author of the study, Martin Kampmann, PhD.
He says: “Using a new CRISPR method we developed, we can uncover how to actually control these microglia, to get them to stop doing toxic things and go back to carrying out their vitally important cleaning jobs.
“This capability presents the opportunity for an entirely new type of therapeutic approach.”
Most of the genes known to increase the risk for Alzheimer’s disease, act through microglial cells.
Kampmann highlights that these cells have a significant impact on how such neurodegenerative diseases play out.
Microglia acts as the brain’s immune system, as ordinary immune cells cannot cross the blood brain barrier.
So, it is left to the healthy microglia to clear out toxins and waste, thus keeping neurons functioning at their best.
When microglia starts to lose their way, it can result in brain inflammation and damage to neurons and the networks they form.
In some instances, microglia will start to remove synapses between neurons.
This may be a normal part of brain development throughout childhood and adolescent years, it can have a catastrophic effect in the brain of an adult.
There have been previous studies which have observed and profiles these varying microglial states, however, they have not been able to characterise the genetics behind them.
Kampmann, along with his team, aim to identify exactly which genes are involved in specific states of microglial activity, and how each of those states are regulated.
If they obtain this knowledge, they could then flip genes on and off, which would set wayward cells back on track.
To accomplish this task, it required surmount fundamental obstacles that have previously prevented researchers from controlling gene expression in these cells.
Microglia, for example, are very resistant to the most common CRISPR technique, which involves getting the desired genetic material into the cell by using a virus to deliver it.
In order to overcome this, Kampmann’s team coaxed stem cells that were donated by human volunteers to become microglia and then confirmed that these cells functioned like their ordinary human counterparts.
The team then developed a new platform that combines a form of CRISPR, which enables researchers to turn individual genes on and off, with read outs of data that indicate functions and states of individual microglia cells.
This analysis enabled Kampmann and his team being able to pinpoint genes that effect the cell’s ability to survive and proliferate, as well as how actively a cell produces inflammatory substances and how aggressively a cell prunes synapses.
As the scientists had determined which genes control those activities, they were able to reset the gees and flip the diseased cell to a healthy state.
Kampmann says that once the right genes have been flipped, it is likely that the microglia that has been repaired will resume their responsibilities, removing neurodegenerative disease and protecting synapses, rather than taking them apart.
The senior author adds: “Our study provides a blueprint for a new approach to treatment.
“It’s a bit of a holy grail.”
