Penn Medicine researchers have developed a selective medicine to get rid of old microglia, while also replenishing them with transplanted surrogate cells in their place, suggesting future potential for treating and even preventing neurodegenerative disorders.
A promising new approach may safely replace microglia—the only members of the immune system in the brain—according to new research conducted in mouse models by neuroscientists at the Perelman School of Medicine and the University of California, Irvine. The researchers used a selective microglia-killing medicine to get rid of old microglia, while also replenishing them with transplanted surrogate cells in their place. These findings, published in the Journal of Experimental Medicine, may hold the potential for treating and even preventing neurodegenerative disorders.
When microglia are healthy, they serve as the central nervous system’s resident front-line disease warriors. But there is evidence they can become dysfunctional in many neurological conditions.
“There is an obstacle because once our own microglia develop in the location where they are supposed to be in our brains, they don’t give up that space,” says F. Chris Bennett, an assistant professor of psychiatry at Penn. “They block the ability to deliver new cells that would take their place. If you want to insert donor microglia, you have to deplete the host microglia to open up room.”
“Our team believed that if we could overcome the brain’s resistance to accepting new microglia, we could successfully transplant them into patients using a safer, more effective process in order to target a great number of diseases,” says co-first author Sonia Lombroso, a Penn Ph.D. student and member of the Bennett Lab. “We decided to investigate whether we could make the donor microglia resistant to the drug that eliminates their host counterparts.”
Approaches could range from fighting disease by replacing dysfunctional microglia with healthy ones to designing microglia that can recognize imminent threats and strike against them with therapeutic proteins before they cause harm.
The Penn-UCI team believes treatments based on this kind of microglial method could be developed within a decade. Their next investigations include studying in animal models how to use the approach to attack the brain plaques associated with Alzheimer’s and other similar diseases.
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