In a world-first, scientists have figured out how to reprogram cells to fight — and potentially reverse — brain diseases like Alzheimer’s.
Researchers at the University of California, Irvine created lab-grown immune cells that can track down toxic brain buildup and clear it away, restoring memory and brain function in mice.
They did this by turning stem cells — which can become any cell in the body — into brain immune cells called microglia.
The edited cells were able to clear the junk without harming healthy tissue, leading to reduced inflammation and a dramatic improvement in brain performance in mice.
The treatment could mark the start of a whole new approach to neurodegenerative disease — with potential applications for brain cancer, multiple sclerosis, and more.
Nearly 7 million Americans are living with Alzheimer’s today, according to the Alzheimer’s Association. Current treatments can only slow symptoms — not reverse them.
Human trials are still several years off, but the early results have scientists buzzing.
If the therapy works in people like it did in mice, it could rewrite the future of brain health, the team said.
The researchers developed this new therapy by turning stem cells into immune cells called microglia (pictured)
The results suggest that the researchers have overcome one of the biggest hurdles to treating degenerative brain diseases: getting medicine past the blood-brain barrier.
This protective layer of cells lines the inner surfaces of the blood vessels inside the brain and functions as a sort of gateway, keeping harmful substances out and keep helpful ones in.
Traditional cell-based treatments have failed to bypass this barrier, but the microglia don’t have to because they are already present inside the brain.
‘We’ve developed a programmable, living delivery system that gets around that problem by residing in the brain itself and responding only when and where it’s needed,’ said co-author and professor of neurobiology Mathew Blurton-Jones in a statement.
Typical microglia both help and hurt the progression of Alzheimer’s disease. When plaque begins to build up in the brain, they spring into action, releasing enzymes to break it down.
But over time, they begin to run amok, triggering inflammation and damaging neurons.
Blurton-Jones and his colleagues found a way to create microglia that treat brain damage without making it worse.
First, they grew human microglia from stem cells, then used CRISPR gene editing — a technique that allows scientists to make precise changes to a cell’s DNA — to reprogram the way they function.
The modified microglia reduced brain plaques (pictured in orange) without damaging neurons and synapses (pictured in green)
Plaques disrupt normal brain function by interfering with cell signaling, thus driving cognitive decline
The modified microglia secrete neprilysin, an enzyme that breaks down brain plaque, only when they are actually near a plaque. This prevents them from accidentally harming critical, healthy parts of the brain.
Plaques disrupt normal brain function by interfering with cell signaling, thus driving cognitive decline.
‘Because the therapeutic protein was only produced in response to amyloid plaques, this approach was highly targeted yet broadly effective,’ said lead-author Jean Paul Chadarevian, a postdoctoral researcher in the Blurton-Jones’ lab.
‘This work opens the door to a completely new class of brain therapies,’ said Robert Spitale, co-author and professor of pharmaceutical sciences.
‘Instead of using synthetic drugs or viral vectors, we’re enlisting the brain’s immune cells as precision delivery vehicles.’
This new therapy could give hope to Alzheimer’s patients and their families, but it will have to go through multiple rounds of rigorous testing before it can be used to treat humans.
The researchers noted that there is still a lot of work to be done to translate their microglial-based therapy into human trials, including demonstrating long-term safety and charting a path toward scalable manufacturing.
But that latter hurdle could be addressed by producing microglia from the patient’s own stem cells, which would also reduce the risk of the immune system rejecting them, according to the researchers.
This has been done to treat other types of diseases, such as blood cancers.
On average, it can take about three to five years for a treatment that’s successful in mice to go to human trials.
