What if damaged brains could be persuaded to make new neurons?
Scientists are exploring that possibility with something considerably smaller than a brain cell. Nanoparticles.
Researchers at the University of South Carolina have developed an engineered polymer nanogel called Nano-ERASER that triggered the production of new neurons in human brain organoids and improved signs of learning and memory in mice with Alzheimer’s disease.
The study, published Aug. 26 in the Cell Press journal Cell Biomaterials, offers an intriguing approach to a disease in which the adult human brain has limited ability to replace neurons lost to degeneration.
The technology works by targeting astrocytes, star-shaped support cells found throughout the central nervous system. Nano-ERASER crosses the blood-brain barrier and delivers antibodies into these cells, where they target a protein called PTBP1.
Reducing PTBP1 prompts astrocytes to reprogram themselves into neurons.
That is an important distinction. Rather than editing DNA, as gene-editing technologies such as CRISPR can, Nano-ERASER uses a reversible cell-reprogramming approach.
“We hope this can be more effective and also safer,” said corresponding author Peisheng Xu, a professor of pharmaceutics at the University of South Carolina.
The researchers first tested the system on human astrocyte cultures and brain organoids designed to mimic Alzheimer’s disease. In both, PTBP1 levels fell and astrocytes converted into functional neurons.
The bigger test came in mice. After treatment, the animals showed improved nesting behavior and performed better in a water maze, suggesting gains in learning and memory. Their brains also showed greater neuron density, along with reduced neuroinflammation and amyloid-beta buildup.
The findings are promising, but a mouse brain is not a human brain. The study does not establish Nano-ERASER as a treatment for Alzheimer’s disease, much less a cure.
The researchers plan longer-term studies and testing in nonhuman primates before any potential human trials.
For now, the nanoparticles have done something valuable. They have given regenerative neuroscience another question worth pursuing.
