Nano-Eraser gel converts astrocytes to
A polymer gel delivering a PTBP1-targeting antibody can transform astrocytes into functional neurons in lab models, improving memory and neuron density in
Scientists have developed a gel that converts brain support cells called astrocytes into neurons, potentially replenishing those lost in Alzheimer's disease. The research, published August 26 in the journal Cell Biomaterials, was led by pharmaceutical scientist Peisheng Xu at the University of South Carolina.
Astrocytes are abundant, star-shaped cells that protect neurons. A key protein for their development is PTBP1. Previous studies suggested eliminating PTBP1 could turn astrocytes into neurons, but later experiments contradicted those findings. Xu's team aimed to resolve the discrepancy.
The Nano-Eraser Technique
Xu employed a technique called Nano-Eraser, developed earlier in his lab. The team packaged an antibody that targets PTBP1 into a polymer gel. This gel helped sneak the antibody across the blood-brain barrier. Once inside astrocytes, the antibody binds to PTBP1 and triggers the cell's machinery to destroy the protein.
Dr. Christiane Wrann, a neuroscientist at Harvard Medical School not involved in the study, told Live Science the approach is "interesting, intriguing and innovative." She highlighted the gel's ability to cross the blood-brain barrier as crucial for brain therapy development.
Laboratory and Organoid Results
The gel was first tested on human astrocytes grown in lab dishes. Over days, these cells lost their star shape and began forming axons. Neuron-specific proteins increased. The cells later exhibited electrical activity, firing synchronously like neurons. Similar results were seen in human stem cell-derived brain organoids.
Effects in Alzheimer's Mouse Models
The researchers then tested the gel in mouse models of Alzheimer's disease. These mice had lost neurons and showed disease features like inflammation, cognitive decline, and sticky protein clumps.
The mice received two intravenous gel doses, eight days apart. Over the next four weeks, behavioral tests suggested treated mice had improved memories and built better nests than untreated mice, indicating better behavioral function. Examination of their brains showed increased neuron density and decreased inflammatory molecules.
However, Xu cautioned that while lab-dish experiments indicated astrocyte conversion, this has not been confirmed in live mice. "We observed that neuron density increased in treated mice compared to untreated ones," he said, "but we cannot yet eliminate the possibility that some other neural stem cells might have also converted into neurons."
Wrann agreed that more experiments are needed to trace if specific astrocytes in the mouse brain changed into neurons. She called the results "intriguing" but noted much more research is required to understand long-term effects on different brain cell types.
Astrocytes themselves serve important functions. Wrann noted a question remains about what "chronically reduced PTBP1 could do to the brain." Xu's team now plans to probe astrocyte conversion further in live mice. Before human clinical trials, safety and effectiveness must be tested in nonhuman primates.
"That's something that needs to be tested step by step," Wrann said.
